Pubmed abstracts for Protein-Protein Interaction search result :

Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.68754393
CONCLUSIONS : In response to PDGF , binding of Ptdlns ( 3 , 4 , 5 ) P 3 and / or Ptdlns ( 3 , 4 ) P 2 to the PH domain of PDK 1 causes its translocation to the plasma membrane where it co localises with PKB , significantly contributing to the scale of PKB activation . . 0.68754393^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.81932543
The same three sites , which all lie in the canonical PKB consensus sequences ( Arg Xaa Arg Xaa Xaa ( Ser / Thr ) ) , became phosphorylated when FKHR was cotransfected with either PKB or PDK 1 ( an upstream activator of PKB ) . 0.81932543^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.62143108
In response to insulin , a PKB mutant with its PH domain deleted ( DeltaPH PKB ) retained the ability to translocate to the plasma membrane when coexpressed with PDK 1 . 0.62143108^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.60407666
PKB is activated by phosphorylation on residues threonine 308 , by the protein kinase PDK 1 , and Serine 473 , by a putative serine 473 kinase . 0.60407666^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :1.6240867
Both events may be promoted by interactions between PDK 1 and phosphorylated or phosphomimetically altered hydrophobic phosphorylation motifs in kinases associated with Akt . 1.6240867^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.62082509
We demonstrate that in platelets PKB is physically associated with PDK 1 and ILK . 0.62082509^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.57211609
The indicating of PDK 1 and PKB as primary targets for discovery of anticancer drugs , together with the observations that both PDK 1 and PKB contain small molecule regulatory binding sites that may be in proximity to the kinase active site , make PDK 1 and PKB ideal targets for the development of new strategies to structure based drug design . 0.57211609^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :1.2416909
Akt interacts with these phospholipids , causing its translocation to the inner membrane , where it is phosphorylated and activated by PDK 1 and PDK 2 . 1.2416909^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
RESULTS : Co expression of p 70 with 3 phosphoinositide dependent protein kinase 1 ( PDK 1 ) , a protein kinase that has previously been shown to phosphorylate and activate protein kinase B ( PKB , also known as c Akt ) , resulted in strong activation of the S 6 kinase in vivo . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Activation of protein kinase B beta and gamma isoforms by insulin in vivo and by 3 phosphoinositide dependent protein kinase 1 in vitro : comparison with protein kinase B alpha . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
The first enzyme in the cascade is termed 3 phosphoinositide dependent protein kinase 1 ( PDK 1 ) , because it only activates protein kinase B ( PKB ) , the next enzyme in the pathway , in the presence of PtdIns ( 3 , 4 , 5 ) P 3 . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Arabidopsis 3 phosphoinositide dependent protein kinase 1 is able to activate human protein kinase B alpha ( PKB / AKT ) in the presence of PtdIns ( 3 , 4 , 5 ) P 3 . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
PKB is regulated by phosphorylation on Thr 308 by 3 phosphoinositide dependent protein kinase 1 ( PDK 1 ) and on Ser 473 by an unidentified kinase . ^^^ Domain swapping used to investigate the mechanism of protein kinase B regulation by 3 phosphoinositide dependent protein kinase 1 and Ser 473 kinase . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
The catalytic domain of serum and glucocorticoid induced protein kinase ( SGK ) is 54 % identical with protein kinase B ( PKB ) and , like PKB , is activated in vitro by 3 phosphoinositide dependent protein kinase 1 ( PDK 1 ) and in vivo in response to signals that activate phosphatidylinositol ( PI ) 3 kinase . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
However , the specific activities of CaM kinase kinase alpha and CaM kinase 2 as to the activation of PKB were more than three orders of magnitude lower than that of 3 phosphoinositide dependent protein kinase 1 ( PDK 1 ) . . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
These studies have both identified an additional PI 3 kinase dependent step within the mast cell degranulation process , possibly involving 3 phosphoinositide dependent protein kinase 1 and a diacylglycerol independent protein kinase C isoform , and shown that the tumor promoting activity of thapsigargin may be due to its activation of protein kinase B and subsequent promotion of cell survival . . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Here we show that expression of a constitutively active mutant of mouse 3 phosphoinositide dependent protein kinase 1 ( PDK 1 ( A280V ) ) in Chinese hamster ovary cells overexpressing the insulin receptor was sufficient to induce PKB phosphorylation at Thr ( 308 ) to approximately the same extent as insulin stimulation . ^^^ Mechanism of phosphorylation of protein kinase B / Akt by a constitutively active 3 phosphoinositide dependent protein kinase 1 . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Further analysis of Akt dephosphorylation revealed that topotecan treatment suppressed upstream kinases of Akt , 3 phosphoinositide dependent protein kinase 1 , and PI ( 3 ) K . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Like PKB , SGK 1 is activated by phosphorylation in response to signals that stimulate phosphatidylinositol 3 kinase , and this is mediated by 3 phosphoinositide dependent protein kinase 1 ( PDK 1 ) and another protein kinase that has yet to be identified . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Thus , we examined the effects of Hsp 90 inhibitors on upstream Akt kinases , phosphatidylinositide 3 OH kinase ( PI3K ) and 3 phosphoinositide dependent protein kinase 1 ( PDK 1 ) . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Studies in rodent cells suggest that atypical PKC ( aPKC ) isoforms ( zeta , lamda , and iota ) and PKB , and their upstream activators , PI3K and 3 phosphoinositide dependent protein kinase 1 ( PDK 1 ) , play important roles in insulin stimulated glucose transport . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Interference with PDK 1 Akt survival signaling pathway by UCN 01 ( 7 hydroxystaurosporine ) . 3 Phosphoinositide dependent protein kinase 1 ( PDK 1 ) plays a central role in activating the AGC subfamily of protein kinases . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Presently , in 3T3 / L1 adipocytes , rosiglitazone induced sizable increases in basal glucose transport that were : dependent on PI3K , 3 phosphoinositide dependent protein kinase 1 ( PDK 1 ) , and PKC lambda ; accompanied by increases in tyrosine phosphorylation of Cbl and Cbl dependent increases in PI3K and PKC lambda activity ; but not accompanied by increases in IRS 1 / 2 dependent PI3K or protein kinase B activity . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Membrane localization of 3 phosphoinositide dependent protein kinase 1 stimulates activities of Akt and atypical protein kinase C but does not stimulate glucose transport and glycogen synthesis in 3T3 L 1 adipocytes . ^^^ It is reported that 3 phosphoinositide dependent protein kinase 1 ( PDK 1 ) is activated in a phosphatidylinositol 3 , 4 , 5 trisphosphate dependent manner and phosphorylates Akt , p70S6 kinase , and atypical protein kinase C ( PKC ) , but its function on insulin signaling is still unclear . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
UCN 01 directly suppressed upstream AKT kinase 3 phosphoinositide dependent protein kinase 1 ( PDK 1 ) ( IC ( 50 ) < 33 nM ) both in vitro and in tumor xenografts . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
PDK 1 ( 3 phosphoinositide dependent protein kinase 1 ) is a member of the AGC ( cAMP dependent , cGMP dependent , protein kinase C ) family of protein kinases , and has a key role in insulin and growth factor signalling through phosphorylation and subsequent activation of a number of other AGC kinase family members , such as protein kinase B . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
PKB / Akt , S6K , SGK and RSK are mediators of responses triggered by insulin and growth factors and are activated following phosphorylation by 3 phosphoinositide dependent protein kinase 1 ( PDK 1 ) . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
To study the function of the PDK 1 ( 3 phosphoinositide dependent protein kinase 1 ) signalling pathway in mediating insulin ' s actions in the liver , we employed CRE recombinase / loxP technology to generate L ( liver ) PDK 1 / mice , which lack expression of PDK 1 in hepatocytes and in which insulin failed to induce activation of PKB in liver . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
In agreement , insulin rapidly induced the phosphorylation of 3 phosphoinositide dependent protein kinase 1 ( PDK 1 ) , protein kinase B ( Akt ) , and mTOR , effects that were prevented by the AG 1024 and LY 294002 . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
The IGF 1 induced Ser 27 phosphorylation did not occur in 3 phosphoinositide dependent protein kinase 1 ( PDK 1 ) deficient embryonic stem cells , but occurred normally in PDK 1 [ L155E ] cells , indicating that the effect of IGF 1 is mediated by PKB . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Both DNA microarray and quantitative RT PCR analysis showed increase in insulin receptor substrate 1 ( Irs 1 ) expression in zinc supplemented cultures , while several key genes downstream of Irs 1 in the insulin signaling pathway , such as protein kinase B ( PKB / Akt ) and 3 phosphoinositide dependent protein kinase 1 ( Pdpk 1 ) did not show significant differences at the transcript level . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
The L 6 cells expressing IR ( Delta 43 ) ( L 6 ( IRDelta 43 ) ) also showed no insulin effect on glucose uptake and glycogen synthase , accompanied by a > 80 % decrease in insulin induction of 3 phosphoinositide dependent protein kinase 1 ( PDK 1 ) activity and tyrosine phosphorylation and of protein kinase B ( PKB ) phosphorylation at Thr ( 308 ) . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Differential roles of phosphoinositide dependent protein kinase 1 and akt 1 expression and phosphorylation in breast cancer cell resistance to Paclitaxel , Doxorubicin , and gemcitabine . 3 Phosphoinositide dependent protein kinase 1 ( PDK 1 ) and Akt 1 are two closely related components of the phosphatidylinositol 3 kinase ( PI3K ) pathway , which is aberrantly regulated in breast cancer . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
CONLCUSIONS : PDK 1 is likely to be one of the protein kinases that mediate the activation of PKB by insulin and growth factors . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
PDK 1 then activates protein kinase B ( PKB ) which , in turn , inactivates glycogen synthase kinase 3 ( GSK 3 ) , leading to the dephosphorylation and activation of glycogen synthase and hence to an acceleration of glycogen synthesis . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
The activation of PKB by insulin appears to involve a novel PtdIns ( 3 , 4 , 5 ) P 3 dependent protein kinase , which we have named PDK 1 . ^^^ The molecular mechanisms underlying PtdIns ( 3 , 4 , 5 ) P 3 stimulated phosphorylation and activation of PKB by PDK 1 are currently under investigation . . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
The homologous site in protein kinase B ( PKB ) , Thr 308 , has been shown to be phosphorylated by the phosphoinositide dependent protein kinase PDK 1 . ^^^ A regulatory link between p70s6k and PKB was demonstrated , as PDK 1 was found to selectively phosphorylate p70s6k at Thr 229 . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Binding of phosphoinositide 3 OH kinase products to the pleckstrin homology domain results in translocation of PKB / Akt to the plasma membrane where it is activated by phosphorylation by upstream kinases including the phosphoinoside dependent kinase 1 ( PDK 1 ) . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Thus , the PKB kinase PDK 1 may be responsible for the phosphorylation of PKC isotypes . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
The serine threonine kinase Akt is a downstream target of phosphoinositide 3 kinase ( PI 3 kinase ) ; it is activated by the phosphoinositide 3 phosphate dependent kinases PDK 1 and PDK 2 . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
First , it binds to the PH domain of PKB , altering its conformation so that it can be activated by PDK 1 . ^^^ Secondly , interaction with PtdIns ( 3 , 4 , 5 ) P 3 recruits PKB to the plasma membrane with which PDK 1 is localized constitutively by virtue of its much stronger interaction with PtdIns ( 3 , 4 , 5 ) P 3 or PtdIns ( 4 , 5 ) P 2 . ^^^ Thirdly , the interaction of PDK 1 with PtdIns ( 3 , 4 , 5 ) P 3 facilitates the rate at which it can activate PKB . . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Phosphoinositide dependent kinase 1 ( PDK 1 ) is at the hub of many signalling pathways , activating PKB and PKC isoenzymes , as well as p 70 S6 kinase and perhaps PKA . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
We recently identified a protein kinase , termed PDK 1 , that phosphorylates PKB at Thr 308 only in the presence of lipid vesicles containing phosphatidylinositol 3 , 4 , 5 trisphosphate ( Ptdlns ( 3 , 4 , 5 ) P 3 ) or phosphatidylinositol 3 , 4 bisphosphate ( Ptdlns ( 3 , 4 ) P 2 ) . ^^^ Expressed PDK 1 and DSTPK 61 phosphorylated Thr 308 of PKB alpha only in the presence of Ptdlns ( 3 , 4 , 5 ) P 3 or Ptdlns ( 3 , 4 ) P 2 . ^^^ Overexpression of PDK 1 in 293 cells activated PKB alpha and potentiated the IGF 1 induced phosphorylation of PKB alpha at Thr 308 . ^^^ Experiments in which the PH domains of either PDK 1 or PKB alpha were deleted indicated that the binding of Ptdlns ( 3 , 4 , 5 ) P 3 or Ptdlns ( 3 , 4 ) P 2 to PKB alpha is required for phosphorylation and activation by PDK 1 . ^^^ CONCLUSIONS : PDK 1 is likely to mediate the activation of PKB by insulin or growth factors . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Coexpression of WT GSK3beta in 293 cells with either PKB alpha ( also known as AKT ) or PDK 1 ( the ' upstream ' activator of PKB ) mimicked the IGF 1 or insulin induced phosphorylation of Ser 9 and inactivation of GSK3beta . . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
The activating mutation in pdk 1 requires akt 1 and akt 2 gene activity in order to suppress the dauer arrest phenotype of age 1 . ^^^ This indicates that the major function of C . elegans PDK 1 is to transduce signals from AGE 1 to AKT 1 and AKT 2 . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Because phosphoinositide dependent kinase 1 ( PDK 1 ) is required for phosphorylation of activation loops of PKC zeta and protein kinase B , we compared their activation . ^^^ Both RO 31 8220 and myristoylated PKC zeta pseudosubstrate blocked insulin induced activation and autophosphorylation of PKC zeta / lambda but did not inhibit PDK 1 dependent ( a ) protein kinase B phosphorylation / activation or ( b ) threonine 410 phosphorylation in the activation loop of PKC zeta . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Moreover , the inhibitory effects of kinase inactive PDK 1 were fully reversed by cotransfection of wild type PDK 1 and partly reversed by wild type PKC zeta , but not by wild type PKB . ^^^ In contrast to the T410A PKC zeta mutant , an analogous double mutant of PKB ( T308A / S473A ) that is resistant to PDK 1 activation had only a small effect on insulin stimulated HA GLUT 4 translocation and did not inhibit HA GLUT 4 translocation induced by overexpression of wild type PDK 1 . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Kinase dead ( KD ) PKB and KD 3 phosphoinositide dependent kinase 1 ( PDK 1 ) cotransfectants acted as dominant negatives because both prevented the insulin induced activation of PKB as well as the inactivation of glycogen synthase kinase 3 , an established substrate of PKB . ^^^ However , the insulin induced activation of PFK 2 was prevented only by KD PDK 1 , but not by KD PKB . ^^^ These results indicate that the insulin induced activation of heart PFK 2 is mediated by a PDK 1 activated protein kinase other than PKB . . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Membrane recruitment driven by lipid second messengers derived from PI 3 kinase leads to PKB phosphorylation and activation by upstream kinases ( PDK 1 and an as yet identified protein kinase ) . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Activated PDK 1 then phosphorylates and activates downstream protein kinases , including protein kinase B ( PKB ) / c Akt , p 70 S6 kinase , PKC isoforms , and serum and glucocorticoid inducible kinase ( SGK ) , thereby eliciting physiological responses . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Phosphoinositide dependent protein kinase 1 ( PDK 1 ) is a recently identified serine / threonine kinase that phosphorylates and activates Akt and p 70 ( S6K ) , two downstream kinases of phosphatidylinositol 3 kinase . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
The PtdIns ( 3 , 4 , 5 ) P 3 dependent activation of protein kinase B ( PKB ) by 3 phosphoinositide dependent protein kinases 1 and 2 ( PDK 1 and PDK 2 respectively ) is a key event in mediating the effects of signals that activate PtdIns 3 kinase . ^^^ The catalytic domain of serum and glucocorticoid regulated protein kinase ( SGK ) is 54 % identical with that of PKB and , although lacking the PtdIns ( 3 , 4 , 5 ) P 3 binding pleckstrin homology domain , SGK retains the residues that are phosphorylated by PDK 1 and PDK 2 , which are Thr 256 and Ser 422 in SGK . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Second , we show that Akt autophosphorylates on the hydrophobic site in vitro : phosphorylation of the activation loop by PDK 1 triggers the phosphorylation of the hydrophobic site in kinase active , but not thermally inactivated , Akt alpha . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Increased phosphorylation of endogenous Akt at threonine 308 was observed in COS 7 cells expressing wild type PDK 1 , but not catalytically inactive PDK 1 , when cellular sphingosine levels were elevated by treatment with sphingomyelinase . ^^^ In this study , we show that p 21 activated kinase 1 , the activity of which is regulated by the GTP bound form of Cdc 42 and Rac and by sphingosine , is phosphorylated by PDK 1 . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Cotransfection with 3 phosphoinositide dependent kinase ( PDK 1 ) , which is required for the full activation of Akt , resulted in enhanced luciferase activity . ^^^ Insulin like growth factor 1 mediated induction of Bcl 2 promoter activity was decreased significantly ( p < 0 . 01 ) by the dominant negative forms of p 85 subunit of PI 3 kinase , PDK 1 , and Akt . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Interaction with PIF converts PDK 1 from a form that phosphorylates PKB at Thr 308 alone to a species capable of phosphorylating Ser 473 as well as Thr 308 . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
We found that PTEN induced growth arrest can be rescued by the co expression of active PI 3K and downstream effectors such as Akt or PDK 1 , and also certain small GTPases such as Rac 1 and Cdc 42 , but not by active Ha ras , raf or RhoA . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
C 2 ceramide did not inhibit ERK , PI3K , or PDK 1 activities and did not alter the translocation of PDK 1 and Akt 1 to the plasma membrane , but blocked nuclear translocation of Akt 1 . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
The PI3K PDK 1 connection : more than just a road to PKB . ^^^ Upon cellular stimulation , PKB is activated through recruitment to cellular membranes by PI3K lipid products and phosphorylation by 3 ' phosphoinositide dependent kinase 1 ( PDK 1 ) . ^^^ We also discuss the evidence that PDK 1 may be involved in the activation of protein kinases other than PKB , the mechanisms by which this activity of PDK 1 could be regulated and the possibility that some of the currently postulated PKB substrates targets might in fact be phosphorylated by PDK 1 regulated kinases other than PKB . . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
PIF increased the rate at which PDK 1 phosphorylated a synthetic dodecapeptide ( T308tide ) , corresponding to the sequences surrounding the PDK 1 phosphorylation site of PKB . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Akt activation requires phosphorylation of Thr ( 308 ) and Ser ( 473 ) by 3 phosphoinositide dependent kinase 1 and 2 ( PDK 1 and PDK 2 ) , respectively . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Phosphoinositide dependent protein kinase 1 ( PDK 1 ) is a recently identified kinase that phosphorylates and activates protein kinase B ( PKB ) . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
In PDK 1 ( / ) ES cells , PKB , p 70 S6 kinase and p 90 Rsk were not activated by stimuli that induced strong activation in PDK 1 ( + / + ) cells . ^^^ The insulin like growth factor 1 ( IGF 1 ) induced PKB phosphorylation at its hydrophobic motif , but not at its T loop residue , in PDK 1 ( / ) cells . ^^^ CONCLUSIONS : PDK 1 mediates activation of PKB , p 70 S6 kinase and p 90 Rsk in vivo , but is not rate limiting for activation of PKA , MSK 1 and AMPK . ^^^ Another kinase phosphorylates PKB at its hydrophobic motif in PDK 1 ( / ) cells . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Vanadate treatment appeared to bypass the requirement for phosphatidylinositol 3 , 4 , 5 trisphosphate when Akt was used as substrate for PDK 1 . ^^^ Tyrosine phosphorylation of PDK 1 by the Abl tyrosine kinase also increased the activity of PDK 1 toward SGK and Akt . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Moreover , dominant interfering alleles of Akt and PDK 1 blocked the zinc induced activation of p70S6k , whereas the lipid kinase activity of PI3K was potently activated by zinc . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Here we report that the major PKB subtype in platelets is PKBalpha , which is activated by phosphorylation of Thr ( 308 ) and Ser ( 473 ) and has a constitutively phosphorylated Thr ( 450 ) that does not contribute to PKB activation . alpha Thrombin and thrombopoietin activate PKBalpha via PI 3K and trigger the concurrent phosphorylation of Thr ( 308 ) ( via PDK 1 ) and Ser ( 473 ) ( via a not yet identified PDK 2 ) . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
However , upstream kinases that activate Akt , such as PDK 1 , also require PIP 3 for activation . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Although we found that EGF stimulated p70s6K phosphorylates through a MAPK dependent and a MAPK independent ( wortmannin sensitive ) pathway , TGF beta 1 failed to block EGF triggered phosphorylation of p70s6K at thr ( 389 ) and thr ( 421 ) / ser ( 424 ) sites , implying that PKB inhibition by TGF beta 1 may result from inhibition of PDK 1 activity instead of inhibition of PI3K activity . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Binding of the pleckstrin homology ( PH ) domain of Akt to membrane PI ( 3 ) P ' s causes the translocation of Akt to the plasma membrane bringing it into contact with membrane bound Akt kinase ( PDK 1 and 2 ) , which phosphorylates and activates Akt . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Upstream regulators of S6K1 and Akt include phosphoinositide 3 kinase ( PI 3 K ) and 3 phosphoinositide dependent kinase 1 ( PDK 1 ) . ^^^ Whereas TPCK had no effect on either mitogen regulated PI 3 K activity or total cellular PDK 1 activity , TPCK prevented phosphorylation of the PDK 1 regulatory sites in S6K1 and Akt . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
To investigate the role of 3 phosphoinositide dependent protein kinase 1 ( PDK 1 ) in the Akt 1 phosphorylation state , wild type ( wt ) PDK 1 and its kinase dead ( kd ) mutant were expressed using an adenovirus gene transduction system in Chinese hamster ovary cells stably expressing insulin receptor . ^^^ The insulin stimulated Akt 1 activity was also enhanced by wt PDK 1 expression but was maintained even at 15 min . ^^^ Interestingly , the insulin stimulated phosphorylation state of Thr 308 was maintained even at 15 min in cells expressing kd PDK 1 , suggesting that kd PDK 1 has a dominant negative effect on dephosphorylation of Thr 308 of Akt 1 . ^^^ These findings suggest that a novel pathway involving dephosphorylation of Akt 1 at Thr 308 by a phosphatase , possibly PP2A , originally , identified as is regulated downstream from PDK 1 , an Akt 1 kinase . . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Inhibition of PDK 1 activity causes a reduction in cell proliferation and survival . 3 Phosphoinositide dependent kinase 1 ( PDK 1 ) was identified by its ability to phosphorylate and activate protein kinase B ( PKB ) in vitro [ 1 , 2 ] and can phosphorylate and activate additional protein kinases in the AGC family in vitro [ 3 6 ] . ^^^ Reduction in PDK 1 levels resulted in inhibition of PKB activity , and a reduction in phosphorylation on Thr 308 and Ser 473 of PKB . p 70 S6 kinase ( p 70 ( S6K ) ) activity was also reduced . ^^^ This study confirms both PKB and p 70 ( S6K ) as in vivo substrates for PDK 1 . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Here we discuss the evidence for inhibition of neutrophil apoptosis via signaling though PI 3 kinase and downstream pathways , including PDK 1 and PKB . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Cyclic AMP inhibits Akt activity by blocking the membrane localization of PDK 1 . ^^^ Binding of 3 ' OH phosphorylated phosphoinositides to the PH domain results in the translocation of Akt to the plasma membrane where it is activated by upstream kinases such as ( phosphoinositide dependent kinase 1 ( PDK 1 ) . ^^^ Here , we show that cAMP has inhibitory effects on the phosphatidylinositol 3 kinase / PDK / Akt signaling pathway . cAMP potently inhibits phosphorylation at threonine 308 and serine 473 of Akt , which is required for the protein kinase activities of Akt . cAMP also negatively regulates PDK 1 by inhibiting its translocation to the plasma membrane , despite not affecting its protein kinase activities . ^^^ Furthermore , when we co expressed myristoylated Akt and PDK 1 mutants which constitutively co localize in the plasma membrane , Akt activity was no longer sensitive to raised intracellular cAMP concentrations . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
We conclude that , at physiological concentrations , TNF alpha activates endogenous PKB by stimulating PDK 2 ( increase in Ser ( 473 ) phosphorylation ) in a PI 3 kinase dependent ( wortmannin sensitive ) manner , without causing detectable stimulation of PDK 1 ( no increase in Thr ( 308 ) phosphorylation ) or ARNO translocation . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
PDK 1 ( 3 ' phosphoinositide dependent kinase 1 ) is thought to participate in Akt activation . ^^^ Overexpression of PDK 1 with the use of an adenovirus vector induced the phosphorylation and activation of Akt ; epsilonKD inhibited , whereas wild type PKCepsilon had no effect on , these actions of PDK 1 . ^^^ These results suggest that epsilonKD inhibits the insulin induced phosphorylation and activation of Akt by interfering with the ability of PDK 1 to phosphorylate Akt . . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
The kinase responsible for phosphorylation of threonine 308 is the PI 3 kinase dependent kinase 1 ( PDK 1 ) , whereas phosphorylation of serine 473 has been suggested to be regulated by PKB / Akt autophosphorylation in a PDK 1 dependent manner . ^^^ Co immunoprecipitation analysis of cell extracts demonstrates that ILK can complex with PKB / Akt as well as PDK 1 and that ILK can disrupt PDK 1 / PKB association . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Phosphatidylinositol 3 kinase ( PI 3 kinase ) inhibition abrogated Ag presentation , suggesting that FcalphaR may trigger a PI 3 kinase dependent signal transduction pathway , and thus phosphatidylinositol dependent protein kinase ( PDK 1 ) and protein kinase B alpha ( PKBalpha ) activation . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
This inositol lipid is an important regulator of cell growth and survival signaling through the Ser / Thr protein kinases PDK 1 and Akt . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
PDK 1 ( a phosphatidylinositol trisphosphate dependent kinase ) and Akt / protein kinase B ( PKB ) activation by insulin showed no difference in B 2 , F 4 , and in control L6hIR cells . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Despite its key role as an upstream activator of enzymes such as protein kinase B and p 70 ribosomal protein S 6 kinase , the regulatory mechanisms controlling PDK 1 activity are poorly understood . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
The PIF binding pocket in PDK 1 is essential for activation of S6K and SGK , but not PKB . ^^^ PDK 1 activates S6K , SGK and PKB isoforms by phosphorylating these kinases at their T loop . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Phosphoinositide dependent kinase 1 ( PDK 1 ) is a serine threonine kinase downstream from PI 3 kinase that phosphorylates and activates other important kinases such as Akt that are essential for cell survival and metabolism . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
PDK 1 regulates growth through Akt and S6K in Drosophila . ^^^ Two key effectors of this pathway are the phosphoinositide dependent protein kinase 1 ( PDK 1 ) and Akt / PKB . ^^^ Although genetic analysis in Caenorhabditis elegans has implicated Akt as the only relevant PDK 1 substrate , cell culture studies have suggested that PDK 1 has additional targets . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
ICAM 2 induced tyrosine phosphorylation of ezrin and PI3K kinase membrane translocation , resulting in phosphatidylinositol 3 , 4 , 5 production , PDK 1 and AKT activation , and subsequent phosphorylation of AKT targets BAD , GSK 3 , and FKHR . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
PI 3K generates phosphatidylinositol 3 , 4 , 5 trisphosphate ( PIP ( 3 ) ) , a lipid second messenger essential for the translocation of PKB / Akt to the plasma membrane where it is phosphorylated and activated by phosphoinositide dependent kinase 1 ( PDK 1 ) and possibly other kinases . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
This effect was correlated with inhibition of the phosphorylation of the PDK 1 downstream substrate Akt / protein kinase B ( PKB ) on two regulatory sites , Thr ( 308 ) and Ser ( 473 ) . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
PDK 1 expressing cells exhibited a high degree of transformation that was associated with the activation of Akt 1 and an elevation of protein kinase Calpha ( PKCalpha ) expression . ^^^ Cells overexpressing Akt 1 did not exhibit anchorage independent growth , whereas PKCalpha overexpression produced significant transformation , although to a lesser extent compared with PDK 1 . ^^^ Isografts of either PDK 1 or PKCalpha expressing cells but not Akt 1 expressing cells in syngeneic mice led to formation of poorly differentiated mammary carcinomas . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
PDK 1 functions as a master kinase , phosphorylating and activating PKB / Akt , S6K and RSK . ^^^ In contrast , hypomorphic PDK 1 mice are viable and fertile , and insulin injection induces the normal activation of PKB , S6K and RSK . ^^^ We provide genetic evidence that PDK 1 is essential for mouse embryonic development , and regulates cell size independently of cell number or proliferation , as well as insulin ' s ability to activate PKB , S6K and RSK . . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Antisense knockout studies and use of a PDK 1 inhibitor showed that neither PKB autophosphorylation nor phosphorylation by PDK 1 accounted for the S 472 phosphorylation in PKCzeta immunoprecipitates . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Mutation of serine 473 to alanine or aspartic acid modulated the degree of threonine 308 phosphorylation in both models , while a point mutation in the substrate binding region of PDK 1 ( L155E ) rendered PDK 1 incapable of phosphorylating PKB . ^^^ Together , these results suggest a mechanism in which 3 ' phosphoinositide lipid dependent translocation of PKB to the plasma membrane promotes serine 473 phosphorylation , which is , in turn , necessary for PDK 1 mediated phosphorylation of threonine 308 and , consequentially , full PKB activation . . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Identification of a plasma membrane Raft associated PKB Ser 473 kinase activity that is distinct from ILK and PDK 1 . ^^^ Here , we report the identification of a constitutively active PKB Ser 473 kinase activity enriched in buoyant , detergent insoluble plasma membrane rafts that are distinct from the cytosolic distribution of PKB and PDK 1 . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
PKB is then activated by the 3 phosphoinositide dependent pro tein kinase 1 ( PDK 1 ) , which like PKB , possesses a PtdIns ( 3 , 4 , 5 ) P3 / PtdIns ( 3 , 4 ) P 2 binding PH domain . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Akt and its activating kinase , PDK 1 , are the only members of the protein kinase A / protein kinase B / protein kinase C like kinase family that are affected by Hsp 90 inhibitors . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
In particular , PDK 1 plays an important role in regulating the Akt survival pathway by phosphorylating Akt on Thr 308 . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
We conclude that S6K1 activity is required for maximal Thr ( 389 ) phosphorylation by mitogens and by multiple phosphatidylinositol 3 kinase dependent inputs including PDK 1 , PKCzeta , and Akt , and we propose that autophosphorylation is an important regulatory mechanism for phosphorylation of the hydrophobic motif Thr ( 389 ) site in S6K1 . . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
The insulin stimulated phosphoinositide 3 kinase ( PI 3 kinase ) / 3 phosphoinositide dependent kinase 1 ( PDK 1 ) / protein kinase B ( PKB ) kinase cascade is believed to play a critical role in metabolic control and cell survival , largely mediated through PKB phosphorylation of many proteins . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
In the biopsies , insulin receptor kinase ( IRK ) activity , insulin receptor substrate ( IRS ) 1 associated phosphatidylinositol 3 kinase ( PI3K ) activity , Ser ( 473 ) and Thr ( 308 ) phosphorylation of protein kinase B ( PKB ) , and protein expression of IRS 1 , IRS 2 , phosphoinositol dependent kinase 1 ( PDK 1 ) , PKB , and GLUT 4 were determined . ^^^ Troglitazone did not alter insulin receptor number or IRS 1 , IRS 2 , PKB , PDK 1 , or GLUT 4 protein expression . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
PDK 1 , an upstream effector of Akt , was also down regulated following CEES exposure , but two other upstream effectors of Akt , PI 3 K and PDK 2 , remained unchanged . 4 . ^^^ The phosphorylation of Akt at Ser ( 473 ) and Thr ( 308 ) was significantly decreased following CEES treatment , reflecting the suppressed kinase activity of both PDK 1 and PDK 2 . 5 . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
We show herein that PPARbeta modulates Akt 1 activation via transcriptional upregulation of ILK and PDK 1 , revealing a mechanism for the control of Akt 1 signaling . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
This effect is associated with a reduction in the phosphorylation and activation of the serine threonine kinases Akt 1 and p 70 S6 kinase ( S6K1 ) , two downstream targets of phosphoinositide dependent kinase 1 ( PDK 1 ) . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
The activated state of the kinase was generated by phosphorylating Thr 309 using PDK 1 and mimicking Ser 474 phosphorylation either with the S474D substitution or by replacing the HM of PKB with that of PIFtide , a potent mimic of a phosphorylated HM . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Recent structural and biochemical work has revealed the basis of phosphorylation regulation of three consecutive protein kinases phosphoinositide dependent kinase 1 ( PDK 1 ) , protein kinase B ( PKB ) / Akt and glycogen synthase kinase 3beta ( GSK3beta ) which transduce signals generated by insulin and / or growth factors binding to cell surface receptors . ^^^ GSK3beta also functions in the developmental Wnt signalling pathway , but without cross talk with the PDK 1 PKB / Akt pathway . ^^^ PDK 1 and PKB are both AGC family kinases . ^^^ Whereas PKB is positively regulated via its phosphorylated C terminal hydrophobic motif , the activity and specificity of PDK 1 are determined by equivalent hydrophobic motifs of substrate AGC kinases . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Expression of a constitutively activated , myristylated Akt or PDK 1 was able to counteract the effect of LO on NF kappa B , whereas constitutively activated Raf was only partially effective . ^^^ Importantly , LO blocked membrane localization of Akt and PDK 1 in Ras transformed cells . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Immunodepleting cytosolic PDK 1 from an in vitro reaction containing plasma membrane and cytosol markedly inhibited insulin stimulated phosphorylation of Akt at the PDK 1 site ( Thr 308 ) but had no effect on phosphorylation at the PDK 2 site ( Ser 473 ) . ^^^ Our data indicate that this PDK 2 activity is the result of a kinase distinct from PDK 1 and is not due to autophosphorylation or transphosphorylation of Akt . . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Fractalkine induced its own expression , via pertussis toxin sensitive G proteins , phosphoinositide 3 kinase ( PI 3 kinase ) , phosphoinositide dependent kinase 1 ( PDK 1 ) , Akt , NIK , IKK and NF kappaB activation , and induced SMC cell cell adhesion and cellular proliferation . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
PI 3 kinase , PDK 1 , and protein kinase B were present in the brush border membrane , where their levels were increased by PMA and blocked by the inhibitors . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
In Cre expressing PDK 1 ( lox / lox ) adipocytes in which the abundance of PDK 1 was reduced by approximately 85 % , the insulin induced phosphorylation both of Akt on threonine 308 and of p 70 S6 kinase on threonine 389 was markedly inhibited . ^^^ The phosphorylation both of Akt on serine 473 and of p 42 and p 44 isoforms of mitogen activated protein kinase induced by insulin was not affected by Cre expression , indicating that the latter specifically inhibits PDK 1 dependent signaling . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Phosphoinositide dependent protein kinase 1 ( PDK 1 ) , also downstream of PI3K , mediates activation of atypical PKC isoforms and Akt . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Association of Akt and PDK 1 with the membrane is also diminished in GqQ209L expressing cardiomyocytes . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
The binding of PKB to PtdIns ( 3 , 4 , 5 ) P3 / PtdIns ( 3 , 4 ) P 2 recruits PKB from the cytosol to the plasma membrane and is also thought to induce a conformational change that converts PKB into a substrate that can be activated by the phosphoinositide dependent kinase 1 ( PDK 1 ) . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Insulin did not activate PKB and S6K , nor did it stimulate 6 phosphofructo 2 kinase and production of fructose 2 , 6 bisphosphate , in the hearts of mPDK 1 ( / ) mice , consistent with PDK 1 mediating these processes . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Increased PDK 1 and phosphorylation of the 85 kDa regulatory subunit of PI 3 kinase , Akt and p70s6k were also observed . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Protein kinase C ( PKC ) alpha , but not Akt 1 , was found previously to be downstream of PDK 1 mediated transformation of mammary epithelial cells . ^^^ To determine the basis for its oncogenic activity , signal transduction pathways mediated by PDK 1 in mammary epithelial cells were investigated . beta Catenin / T cell factor dependent promoter activity was markedly activated in PDK 1 and PKCalpha expressing cells , but not in Akt 1 expressing cells , which resulted in increased levels of the beta catenin / T cell factor target genes c myc and cyclin D 1 . ^^^ In contrast , caveolin 1 , of which the transcription is suppressed by c myc , was down regulated in PDK 1 and PKCalpha expressing , but not in Akt 1 expressing cells . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Many of the genes appear to act in the insulin branch of the dauer pathway , including pdk 1 , akt 1 , aex 6 , and hid 1 . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
New insights into downstream signalling mechanisms , including the activation of STAT 3 , PDK 1 and Akt , further corroborate the importance of Src family kinases in tumorigenesis and chemoresistance . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Short myristoylated peptides were derived from the target regions of the tyrosine kinases c Kit and Lyn and the serine / threonine kinases 3 phosphoinositide dependent kinase 1 ( PDK 1 ) and Akt / protein kinase B ( PKB ) . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Treatment with antisense PDK 1 oligonucleotides reduces PDK 1 expression and inhibits the stimulation of Akt phosphorylation by p 65 . ^^^ Pharmacological inhibition of PI 3 kinase blocks both PDK 1 and Akt phosphorylation by p 65 , placing PI 3 kinase upstream of PDK 1 in the signaling cascade leading to increased Akt phosphorylation . ^^^ However , neither inhibition of PI 3 kinase or of PDK 1 affected the ability of p 65 to stimulate Akt expression , suggesting that distinct mechanisms underlie the two stimulatory effects of p 65 on Akt . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Paks are activated directly by the small GTPases Rac and Cdc 42 and several protein kinases including Akt and PDK 1 . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Akt , a kinase downstream of PDK 1 , is phosphorylated and concentrates in the membrane fraction within 5 min of TGF beta 1 treatment . ^^^ Thus , although the PI3K PDK 1 Akt pathway alone is insufficient to stimulate COL1A2 gene transcription , its activation by TGF beta 1 enhances Smad 3 transcriptional activity leading to increased collagen 1 expression in human mesangial cells . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Moreover , IGF 1 induced phosphorylation of endogenous WNK 1 did not occur in PDK 1 / ES ( embryonic stem ) cells , in which PKB is not activated . ^^^ In contrast , IGF 1 still induced normal phosphorylation of WNK 1 in PDK 1 ( L155E / L155E ) knock in ES cells in which PKB , but not S6K ( p 70 ribosomal S 6 kinase ) or SGK 1 ( serum and glucocorticoid induced protein kinase 1 ) , is activated . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
CXCL 16 mediated NF kappa B activation occurred via heterotrimeric G proteins , PI3K , PDK 1 , Akt , and 1 kappa B kinase ( IKK ) . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Integrin linked kinase ( ILK ) , phosphoinositide dependent kinase ( PDK 1 ) , and PKB are implicated in the MMP 2 increase . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Examination of the phosphatidylinositol 3 kinase ( PI 3 K ) / Akt signaling cascade revealed higher activities of PDK 1 and Akt but not PI 3 K in cav 1 stimulated cells compared to control cells . ^^^ Analysis of potential substrates for PP 1 and PP2A revealed that cav 1 mediated inhibition of PP 1 and PP2A leads to increased PDK 1 , Akt , and ERK1 / 2 activities . ^^^ We demonstrate that increased Akt activities are largely responsible for cav 1 mediated cell survival using dominant negative Akt mutants and specific inhibitors to MEK1 / MEK and show that cav 1 increases the half life of phosphorylated PDK 1 and Akt after inhibition of PI 3 K by LY 294002 . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
After a single ECS , the phosphorylation of Akt was increased , as were the signals detected by phospho PDK 1 substrate antibody , which suggests the activation of PDK 1 , an upstream molecule of Akt . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
ERK1 / 2 co immunoprecipitated with Akt in a multimolecular assembly of signaling molecules , containing at a minimum ERK1 / 2 , Akt , Rsk , and 3 phosphoinositide dependent kinase 1 ( PDK 1 ) . ^^^ We hypothesize that the kinase Rsk , whose activation requires phosphorylation by both ERK1 / 2 and PDK 1 , acts as a bridge bringing ERK1 / 2 into proximity with PDK 1 associated Akt . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
This treatment also increased PI 3 kinase activation , PDK 1 expression , Akt phosphorylation and p70s6k phosphorylation . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
In all , HRG stimulated glucose transport in muscle cells by activation of a pathway that requires PI3K , PDK 1 , and PKCzeta , but not PKB , and that shows cross talk with the MAPK pathway . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
PDK 1 activity towards protein kinase B ( PKB ) is partially regulated by its pleckstrin homology ( PH ) domain , which preferentially binds to 3 phosphoinositides . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
We show that the Ft 1 protein interacts directly with PKB , enhancing the phosphorylation of both of its regulatory sites by promoting its interaction with the upstream kinase PDK 1 . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Finally , in a proof of principle pathway wide cell based genetic screen , conducted to detect negative genetic regulators of Akt S 473 phosphorylation , both known negative regulators of this phosphorylation , PTEN and PDK 1 , were found . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Celecoxib and DMC block Akt activation in PC 3 cells through the inhibition of phosphoinositide dependent kinase 1 ( PDK 1 ) with IC ( 50 ) of 48 and 38 micro M , respectively . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Upon estradiol exposure , we observed an enhanced phosphorylation of the proteins involved in the phosphatidylinositol 3 OH kinase ( PI3K ) / Akt pathway like PDK 1 , Akt , GSK 3 , Bcl 2 , together with ERK1 / 2 , which was also involved in cell survival signals . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Insulin induced translocation of PDK 1 to the plasma membrane , phosphorylation of Akt and p70S6 kinase and ribosomal protein S 6 , increase in the amount of 4E BP 1 gamma form , association of eIF4E with eIF4G , and protein synthesis were decreased by overexpression of wild type SHIP 2 by adenovirus mediated gene transfer . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Phosphorylation of the Src and Rac effector p 21 activated protein kinase ( PAK ) 1 on Thr 423 ( the phosphoinositide dependent kinase 1 [ PDK 1 ] site ) was attenuated by ROS inhibition , and infection of VSMCs with dominant negative PAK 1 adenovirus attenuated migration . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
It was recently shown that RSK 2 recruits PDK 1 , the kinase responsible for both Akt and RSK activation . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
In the knockin cells , protein kinase B ( PKB ) was not activated by IGF 1 , whereas ribosomal S 6 kinase ( RSK ) was activated normally , indicating that PtdIns ( 3 , 4 , 5 ) P 3 binding to PDK 1 is required for PKB but not RSK activation . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Immunocytochemical studies showed that p 70 ( S6K ) , Akt 1 , PDK 1 , and p 85 phosphoinositide 3 kinase ( PI 3 kinase ) were localized to the actin arc , a caveolin enriched cytoskeletal structure located at the leading edge of migrating cells . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
The phosphatidylinositide 3 OH kinase / 3 phospho inositide dependent protein kinase 1 ( PDK 1 ) / Akt and the Raf / mitogen activated protein kinase ( MAPK / ERK ) kinase ( MEK ) / mitogen activated protein kinase ( MAPK ) pathways have central roles in the regulation of cell survival and proliferation . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
The authors describe the development and optimization of an Immobilized Metal Assay for Phosphochemicals ( IMAP ) based couple d assay using PDK 1 and inactive Akt 2 enzymes . ^^^ PDK 1 phosphorylates Akt 2 at Thr 309 in the catalytic domain , leading to enzymatic activation . ^^^ Activation of Akt by PDK 1 is measured by quantitating the phosphorylation of Akt specific substrate peptide using the IMAP assay format . ^^^ This coupled assay has the potential to identify compounds that target the inactive form of Akt and prevent its activation by PDK 1 , in addition to finding inhibitors of PDK 1 and activated Akt enzymes . . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
On the other hand , protein levels and phosphorylation of PDK 1 and Akt were decreased in retina of both mice . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
A critical component of this pathway is 3 phosphoinositide dependent kinase 1 ( PDK 1 ) , a PH domain containing enzyme that catalyzes the activating phosphorylation for many AGC kinases , including Akt and protein kinase C isozymes . ^^^ The interaction of PDK 1 with Grb 14 facilitates Akt function : disruption of the interaction by overexpression of a construct of Grb 14 mutated in the PDK 1 binding motif significantly decreases insulin dependent activation of Akt . ^^^ Thus , Grb 14 serves as an adaptor protein to recruit PDK 1 to activated insulin receptor , thus promoting Akt phosphorylation and transduction of the insulin signal . . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
IBOP costimulation suppressed nitric oxide ( NO ) release from VEGF treated EC through decreased activation of Akt , eNOS , and PDK 1 . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Full activation of protein kinase B ( PKB ) / Akt requires phosphorylation on Thr 308 and Ser 473 by 3 phosphoinositide dependent kinase 1 ( PDK 1 ) and Ser 473 kinase ( S473K ) , respectively . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Once activated PI3Ks generate phosphatidylinositols ( PtdIns ) ( 3 , 4 , 5 ) P ( 3 ) leading to the recruitment and activation of Akt / protein kinase B ( PKB ) , PDK 1 and monomeric G proteins ( e . g . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Tumors exhibited increased association of Egfr with clathrin heavy chain ( CHC ) , Gab 1 , and p85alpha , the regulatory subunit of phosphoinositide 3 kinase ( PI3K ) , and tumors also overexpressed c Src , PDK 1 , and Akt . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
IGF 1 dependent GSK 3 beta phosphorylation and the resulting GSK 3 beta inactivation were mediated by activation of a PI 3 kinase dependent , phosphoinositide dependent kinase 1 ( PDK 1 ) dependent , and Akt dependent mechanism . ^^^ IGF 1 dependent inhibition of apoptosis , similar to GSK 3 beta activity , was mediated by a PI 3 kinase , PDK 1 , and Akt dependent mechanism . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Membrane bound Akt is then phosphorylated at two sites for its full activation ; Thr 308 in the activation loop of the kinase domain is phosphorylated by 3 phosphoinositide dependent kinase 1 ( PDK 1 ) and Ser 473 in the C terminal hydrophobic motif by a putative kinase PDK 2 . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
In addition to inhibiting kinase activity of individual Akt isoforms , both inhibitors blocked the phosphorylation and activation of the corresponding Akt isoforms by PDK 1 ( phosphoinositide dependent kinase 1 ) . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Insulin also induced the phosphorylation of FLNc at Ser 2213 in cardiac muscle in vivo , but not in cardiac muscle that does not express PDK 1 ( 3 phosphoinositide dependent kinase 1 ) , the upstream activator of PKB . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
EGF dependent activation of the Erk1 / 2 pathway and the upstream activators of Akt ( Gab 1 , erbB 3 , PI 3 kinase , and PDK 1 ) showed no density dependency . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Western blot analysis indicated that polysaccharides stimulated the phosphorylation of PDK 1 ( Serine 241 ) and Akt ( Threonine 308 ) . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Apoptosis and cell cycle arrest appeared to be independent of derivative induced inhibition of PDK 1 and phosphorylation of Akt and Erk1 / 2 . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Treatment of breast cancer cells that overexpress HER 2 with trastuzumab inhibited HER 2 HER3 association , decreased PDK 1 activity , reduced Thr 308 and Ser 473 phosphorylation of AKT , and reduced AKT enzymatic activity . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Investigation of proteins in the phosphatidylinositol 3 ' kinase / Akt signaling pathway in PTEN delivered mouse lung revealed that the PTEN protein was highly expressed , whereas the protein levels of PDK 1 , total Akt 1 , phospho ( Thr 308 ) Akt , phospho ( Ser 2448 ) mTOR , p70S6K , and 4E BP 1 were decreased to varying degrees . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
In agreement with the previous observation that DN Akt inhibits migration of Pten ( / ) cells , we demonstrate here that overexpression of KD PDK 1 , the Akt kinase , reduces Pten ( / ) cell migration . ^^^ Furthermore , overexpression of DN forms of Akt , Rac , or PDK 1 , all of which inhibit migration of Pten ( / ) cells , had no effect on cortical actin accumulation . ^^^ Our findings suggest that PDK 1 / Akt signaling pathway plays a major role in regulating cell migration induced by PTEN deficiency . . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Phosphoinositide 3 kinase ( PI 3 kinase ) and its downstream signaling molecules PDK 1 and Akt were analyzed in SK N SH and SK N BE ( 2 ) human neuroblastoma cell lines . ^^^ When cells were stimulated with insulin , PI 3 kinase was activated in both cell lines , whereas the translocation of PDK 1 to the membrane fraction and phosphorylated Akt were observed only in SK N SH cells . ^^^ When SK N SH cells were pretreated with the NADPH oxidase inhibitor diphenyleneiodonium chloride before insulin stimulation , insulin mediated translocation of PDK 1 to the membrane fraction and phosphorylation of Akt were remarkably reduced , whereas PI 3 kinase activity was not changed significantly . ^^^ These results indicate that not only PI 3 kinase activation but also inhibition of PTEN by ROS is needed to increase cellular level of phosphatidylinositol 3 , 4 , 5 trisphosphate for recruiting downstream signaling molecules such as PDK 1 and Akt in insulin mediated signaling . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
The RAS activated RAF > MEK > extracellular signal regulated kinase ( ERK ) and phosphatidylinositol 3 ' kinase ( PI3 ' kinase ) > PDK 1 > AKT signaling pathways are believed to cooperate to promote the proliferation of normal cells and the aberrant proliferation of cancer cells . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Pharmacological inhibition or knockdown studies revealed that IL 18 induced cardiomyocyte hypertrophy and ANF gene transcription via PI3K , PDK 1 , Akt , and GATA 4 . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
They further support that PDK 2 is a molecule distinct from PDK 1 and Akt , and that PDK 2 activity is not sufficient for the full activation of Akt in the absence of PDK 1 activity . . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Although PDK 1 phosphorylates and activates PKC , PKB , and RSK in vivo , PDK 1 regulation of PKA remains controversial . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Here we show that components of this pathway , including Akt , GSK3beta and PDK 1 , are more highly phosphorylated in the brains of Pcmt 1 / mice , particularly in cells of the hippocampus , in comparison with Pcmt1+ / + mice . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
EGF increased PI 3 kinase activity resulting in stimulation of PDK 1 and Akt kinase activities . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Activated forms of H RAS and K RAS differentially regulate membrane association of PI3K , PDK 1 , and AKT and the effect of therapeutic kinase inhibitors on cell survival . ^^^ In HCT 116 H RAS V 12 cells , PI3K , PDK 1 , and AKT were membrane associated , whereas in parental cells expressing K RAS D 13 , only PDK 1 was membrane bound . ^^^ Collectively , our data argue that molecular inhibition of AKT and PDK 1 signaling enhances the radiosensitivity of HCT 116 cells expressing H RAS V 12 but not K RAS D 13 . ^^^ Small molecule inhibitory agents that blocked stimulated and / or basal PDK 1 and AKT function profoundly reduced HCT 116 cell survival but had variable effects at enhancing tumor cell radiosensitivity . . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Akt / PKB activation requires the phosphorylation of Thr 308 in the activation loop by the phosphoinositide dependent kinase 1 ( PDK 1 ) and Ser 473 within the carboxyl terminal hydrophobic motif by an unknown kinase . ^^^ The rictor mTOR complex directly phosphorylated Akt / PKB on Ser 473 in vitro and facilitated Thr 308 phosphorylation by PDK 1 . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Akt is activated by the phosphorylation of 3 phosphoinositide dependent kinase 1 ( PDK 1 ) . ^^^ To address this issue , we treated bovine eNOS stably transfected human embryonic kidney 293 cells with Hsp 90 inhibitors and determined the alterations of phospho eNOS , Akt , and PDK 1 . ^^^ Silencing the PDK 1 gene by small interfering RNA was sufficient to induce reduction of phospho Akt and consequent loss of serine 1179 phosphorylated eNOS . ^^^ Moreover , overexpression of PDK 1 , but not Akt , reversed Hsp 90 inhibition induced loss of eNOS serine 1179 phosphorylation and salvaged enzymatic activity . ^^^ Thus , in addition to functioning as a module to recruit Akt to eNOS , Hsp 90 also critically stabilized PDK 1 by preventing it from proteasomal degradation . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Phosphoinositide dependent phosphorylation of PDK 1 regulates nuclear translocation . 3 phosphoinositide dependent kinase 1 ( PDK 1 ) phosphorylates the activation loop of a number of protein serine / threonine kinases of the AGC kinase superfamily , including protein kinase B ( PKB ; also called Akt ) , serum and glucocorticoid induced kinase , protein kinase C isoforms , and the p 70 ribosomal S 6 kinase . ^^^ PDK 1 contains a carboxyl terminal pleckstrin homology domain , which targets phosphoinositide lipids at the plasma membrane and is central to the activation of PKB . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Here , we demonstrate that the enhanced AIG ( eAIG ) correlates with increased activation levels of phosphatidylinositol 3 kinase ( PI3K ) and not with changes in the protein levels of the p 85 regulatory subunit of PI3K , PDK 1 or PTEN modulators , and / or mediators of PI3K activity . eAIG could be blunted selectively by treatment with the PI3K inhibitor , LY 294002 , or by overexpression of either the PI3K antagonist , PTEN , dominant interfering alleles of PI3K or a downstream PI3K mediator , AKT , but not by the MEK inhibitor , PD 98059 , dominant interfering alleles of MEK or the signal transducer and activator of transcription ( STAT ) 3 . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
In this study , we examined the involvement of Akt / PKB and its upstream kinase , PDK 1 and whether JNK activation correlated with human and rat VSMC apoptosis induced by staurosporine and by c myc , respectively . ^^^ Further , whereas transient expression of phosphorylated Akt protected VSMCs from apoptosis by nearly 50 % , expression of dominant interfering alleles of Akt or PDK 1 strongly inhibited IGF 1 mediated VSMC survival . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
RESULTS : In the hypertrophic muscle of MLC / mlgf 1 mice , we observed increased phosphorylation of phosphoinositide dependent protein kinase 1 ( PDK 1 ; 53 % increase ) , the mammalian target of rapamycin ( mTOR ; 112 % increase ) , and p 70 S6 kinase ( p70S6K ) ( 254 % increase ) but no significant change in Akt phosphorylation ( 4 % decrease ) . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Role of the PDK 1 PKB GSK 3 pathway in regulating glycogen synthase and glucose uptake in the heart . ^^^ In order to investigate the importance of the PDK 1 PKB GSK 3 signalling network in regulating glycogen synthase ( GS ) in the heart , we have employed tissue specific conditional knockout mice lacking PDK 1 in muscle ( mPDK 1 / ) , as well as knockin mice in which the protein kinase B ( PKB ) phosphorylation site on glycogen synthase kinase 3alpha ( GSK3alpha ) ( Ser 21 ) and GSK3beta ( Ser 9 ) is changed to Ala . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
This effect was correlated with inhibition of the phosphorylation of the PDK 1 downstream substrate Akt / protein kinase B ( PKB ) . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
The phosphoinositide 3 kinase / 3 phosphoinositide dependent kinase 1 ( PDK 1 ) / Akt signaling pathway plays a key role in cancer cell growth , survival , and tumor angiogenesis and represents a promising target for anticancer drugs . ^^^ A number of cancer cell lines with elevated Akt activity were > 30 fold more sensitive to growth inhibition by PDK 1 inhibitors in soft agar than on tissue culture plastic , consistent with the cell survival function of the PDK1 / Akt signaling pathway , which is particularly important for unattached cells . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
DeltaPH PKB EEE was expressed in E . coli together with PDK 1 , the kinase responsible for phosphorylating PKB at T 308 , which was expressed as a GST fusion . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Thrombin and active PAKT423E phosphorylated p 38 MAP kinase ( p38MAPK ) , ERK1 / 2 , phosphatidylinositol dependent kinase 1 ( PDK 1 ) and protein kinase B / Akt ( PKB ) whereas kinase deficient PAK 1 prevented activation of these kinases by thrombin . ^^^ In addition , kinase deficient MKK 3 inhibited activation of PDK 1 and PKB by thrombin . ^^^ Moreover , kinase deficient MKK 3 , PDK 1 and PKB inhibited thrombin and PAK dependent TF expression and promoter activity . ^^^ Together these findings show that PAK is a critical element of thrombin signalling in PASMC which is involved in the regulation of TF expression by sequentially activating MKK3 / p38MAPK , PDK 1 and PKB . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Remarkably , transfection of HepG 2 cells with vectors expressing a dominant negative PDK 1 or the PKB inhibitor , TRB 3 , did not influence while dominant negative Raf inhibited the IGF 1 effect on HIF 1alpha . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
In summary , both the antiproliferative and apoptotic effects of gamma tocotrienol appear to be mediated by a reduction in the Pl3K / PDK 1 / Akt signaling , an important pathway associated with cell proliferation and survival in neoplastic mammary epithelial cells . . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Akt inhibitory phenoxazines did not inhibit the activity of recombinant phosphatidylinositol 3 ' kinase , PDK 1 , or SGK 1 but potently inhibited the kinase activity of recombinant Akt and Akt deltaPH , a mutant lacking the pleckstrin homology domain . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
In addition , FAK , Akt , PDK 1 , GSK 3beta , BAD , and PTEN were phosphorylated by ICAM 3 overexpression , resulting in enhanced cell proliferation . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Cells lacking PDK 1 show decreased activity of these protein kinases , including protein kinase B ( PKB ) and p70S6K , whereas mTOR activity remains largely unaffected . ^^^ We show that PKB activity is a critical downstream component of PDK 1 in mediating translation of cystatin C , RANKL , and Rab11a , whereas mTOR activity is less important for effective translation of these targets . . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Pharmacological inhibitors of the phosphatidylinositol 3 kinase , Akt , and PDK 1 also abrogated the retinoid stimulated increase in steroid sulfatase activity in HL 60 cells . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Consistent with the presence of a complete PI 3K signaling pathway in the nucleus , we have recently found that phosphoinositide dependent kinase 1 ( PDK 1 ) , a kinase functioning downstream of PI 3K and upstream of Akt , is a nucleo cytoplasmic shuttling protein . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
The association of PKB with 3 ' phosphoinositide dependent kinase 1 ( PDK 1 ) , a kinase that phosphorylates PKB at Thr 308 , and PDK 1 abundance were higher in 7 than in 26 d old pigs . ^^^ The result suggests that the developmental change in PKB activation is isoform specific and involves regulation by PDK 1 . . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
The IkappaB kinase ( IKK ) / NF kappaB and phosphatidylinositol 3 OH kinase / 3 phosphoinositide dependent protein kinase 1 ( PDK 1 ) / Akt pathways regulate various cellular functions , especially cell survival . ^^^ Here we show that PDK 1 can activate IKK / NF kappaB signaling in addition to Akt signaling to promote cell survival . ^^^ Screening kinases that could modulate NF kappaB activity revealed that expression of an upstream Akt kinase PDK 1 up regulates NF kappaB transcriptional activity . ^^^ Akt , which was previously reported to activate IKKalpha , did not participate in the PDK 1 dependent IKKbeta or NF kappaB activation . ^^^ These results indicate that PDK 1 is a critical regulator of cell survival by modulating the IKK / NF kappaB pathway in addition to the Akt pathway . . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Kinase assays and the phosphorylation of AKT , GSK 3alpha / beta , PDK 1 , ERK1 / 2 , SGK , p 38 , FAK , EGFR , JAK 2 , PKC isoforms , and the cleavage of poly ( ADP ribose ) polymerase ( PARP ) were examined in treated and untreated cell lines . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
The knockin ES cells were viable , mutant PDK 1 was expressed at normal levels and IGF 1 induced activation of protein kinase B ( PKB / Akt ) , which is a PDK 1 substrate that does not require hydrophobic motif phosphorylation to be activated . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Akt is activated by growth factors via a phosphorylation dependent pathway involving the kinases phosphoinositide 3 ( PI 3 ) kinase and phosphoinositide dependent protein kinase 1 ( PDK 1 ) and is negatively regulated by phosphatase and tensin homolog deleted on chromosome 10 ( PTEN ) . ^^^ Hypothermia may protect from ischemic damage in part by preserving Akt activity and attenuating the apoptotic effects of PTEN , PDK 1 , and FKHR . . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
We explored the importance of PDK 1 , the protein kinase that activates PKB and S6K , in mediating tumorigenesis caused by the deletion of PTEN . ^^^ Our findings provide genetic evidence that PDK 1 is a key effector in mediating neoplasia resulting from loss of PTEN and also validate PDK 1 as a promising anticancer target for the prevention of tumors that possess elevated PKB and S6K activity . . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Several recent reports have brought conclusive evidence that the tumor suppressor PTEN , once considered a strictly cytoplasmic protein , shuttles to the nuclear compartment , where it joins a variety of components of the same pathway it regulates in the cytoplasm , among which PI3K , PDK 1 and AKT . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Additional studies showed that treatment with cytotoxic doses of alpha tocotrienol decreased total , membrane , and cytosolic levels of FLIP , and reduced phosphorylated PDK 1 ( active ) and phosphorylated Akt ( active ) levels in these cells . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Further studies demonstrated that cAMP inhibited FBS induced membrane localization of 3 phosphoinositide dependent kinase 1 ( PDK 1 ) which is a required process for PDK 1 to phosphorylate Akt , but had no significant effect on phosphoinositide 3 kinase activity . ^^^ These results indicate that cAMP inhibition of proliferation of HCC cells is mediated by Akt and cAMP inhibits Akt activation via blocking membrane localization of PDK 1 . . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
These included proteases , dauer pathway genes ( akt 1 , pdk 1 & daf 7 ) and aging and stress resistance genes such as superoxide dismutase ( sod 4 ) , heat shock genes ( hsp 4 & hsp 6 ) , and eat genes , and signaling proteins like G protein coupled receptors , regulators of G protein signaling ( rgs ) , and serine / threonine kinases . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Octreotide treatment decreased the tyrosine phosphorylation levels of the PI3K regulatory subunit p 85 , induced dephosphorylation of phosphoinositide dependent kinase 1 ( PDK 1 ) and Akt , and activated glycogen synthase kinase 3beta ( GSKbeta ) . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
As such , it has been postulated that PDK 1 / Akt signaling inhibitors may hold promise as novel therapeutic agents for pancreatic cancer . ^^^ Previous studies have demonstrated that OSU 03012 , a celecoxib derivative , specifically inhibits PDK 1 mediated phosphorylation of Akt with IC ( 50 ) values in the low muM range . ^^^ Treatment with OSU 03012 resulted in decreased PDK 1 mediated Akt phosphorylation and cell growth inhibition for all cell lines with IC ( 50 ) values ranging between 1 . 0 and 2 . 5 muM . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Inhibitors of individual components , such as PI3K , PDK 1 , Akt , and mTOR , are being developed at a rapid pace and have promise for improving the care of cancer patients . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Elevated phosphorylation and activation of PDK 1 / AKT pathway in human breast cancer . ^^^ The phosphorylation of FAK , mTOR , p70S6K , and PDK 1 were elevated in both breast cancer cell lines , whereas the phosphorylation of AKT , EGFR , ErbB2 / Her2 , PDGFR , Shc , and Stat 3 were elevated in only one breast cancer line compared to normal primary mammary epithelial cells and telomerase immortalised breast epithelial cells . ^^^ Consistent findings were obtained as greater than 70 % of invasive breast carcinomas expressed moderate to high levels of phosphorylated PDK 1 , AKT , p70S6K , and EGFR . ^^^ Elevated phosphorylation of PDK 1 , AKT , mTOR , p70S6K , S 6 , EGFR , and Stat 3 were highly associated with invasive breast tumours ( P < 0 . 05 ) . ^^^ This is the first report demonstrating phosphorylation of PDK 1 is frequently elevated in breast cancer with concomitantly increased phosphorylation of downstream kinases , including AKT , mTOR , p70S6K , S 6 , and Stat 3 . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
The signaling upstream of eNOS involving Akt and PDK 1 were also suppressed by the HCMV infection . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Mechanistically , mahanine inhibited cell survival pathway by dephosphorylation of PIP 3 dependent kinase 1 ( PDK 1 ) thereby deactivation of Akt and downregulation of Bcl xL . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
We recently reported that phosphoinositide dependent kinase 1 ( PDK 1 ) partially corrects the defect in IL 4 production present in CD 28 deficient T cells , suggesting that PDK 1 regulates IL 4 independently of Akt . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
PDK 1 phosphorylates endosome associated SGK 3 at Thr 320 , whereas diversion of SGK 3 to the plasma membrane , where PDK 1 normally activates PKB , interferes with PDK 1 phosphorylation of SGK 3 . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Here , we show for the first time that , in normal muscle cells subjected to oxidative stress , the phosphatidylinositol ( 3 ) kinase ( PI ( 3 ) kinase ) associated proteins PDK 1 and Akt associate with caveolae where they bind to caveolin 3 , and that normal activation of this pathway promotes cell survival . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Although Pak is primarily activated by Rac and Cdc 42 , there are additional proteins that regulate Pak activity and localization , including three AGC protein kinase family members , Akt 1 , PDK 1 , and cAMP dependent protein kinase . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Although the suppression of phospho Akt by selenium has been reported previously , little information is available on whether selenium modulates primarily the PI3K phosphoinositide dependent kinase 1 ( PDK 1 ) side of Akt phosphorylation or the phosphatase side of Akt dephosphorylation . ^^^ Our results showed that selenium decreased Akt phosphorylation at Thr 308 ( by PDK 1 ) and Ser 473 ( by an unidentified kinase ) ; the Thr 308 site was more sensitive to selenium inhibition than the Ser 473 site . ^^^ However , the activity of PI3K was reduced by 30 % in selenium treated cells , thus discouraging the recruitment of PDK 1 and Akt to the membrane due to low phosphatidylinositol 3 , 4 , 5 trisphosphate formation by PI3K . ^^^ Consistent with the above interpretation , the membrane localization of PDK 1 and Akt was significantly diminished as shown by Western blotting . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
KP 372 1 directly inhibited the kinase activity of AKT , PDK 1 , and FLT 3 in a concentration dependent manner . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Phosphorylated PDK 1 is an activator of Akt by phosphorylating Akt . ^^^ Curcumin reduced phosphorylation of PDK 1 and inhibited constitutive activation of Akt . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Upstream regulators of S6K , such as PDK 1 and protein kinase B ( PKB / Akt ) , are recruited to the membrane via their pleckstrin homology ( PH ) or protein protein interaction domains . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Following confirmation of the natural history of this leukemia in the transgenic mice , we demonstrated that the transformed murine lymphocytes express relevant therapeutic targets ( Bcl 2 , Mcl 1 , AKT , PDK 1 , and DNMT 1 ) , wild type p 53 status , and in vitro sensitivity to therapeutic agents relevant to the treatment of human CLL . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Mutants of ins 1 , daf 2 , age 1 , pdk 1 , and akt 1 , which encode the homologs of insulin , insulin / IGF 1 receptor , PI 3 kinase , phosphoinositide dependent kinase , and Akt / PKB , respectively , show severe defects in salt chemotaxis learning . daf 2 and age 1 act in the ASER salt sensing neuron , and the activity level of the DAF 2 / AGE 1 pathway in this neuron determines the extent and orientation of salt chemotaxis . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Protein kinase Cdelta participates in insulin induced activation of PKB via PDK 1 . ^^^ Insulin also increased the physical association between PKCdelta with PKB and with PDK 1 . ^^^ PKB PKCdelta association was accounted for by the involvement of PDK 1 . ^^^ Overexpression of dominant negative PKCdelta abrogated insulin induced association of PKCdelta with both PKB and PDK 1 . ^^^ The results indicate that insulin activated PKCdelta interacts with PDK 1 to regulate PKB . . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
Two mutations were gain of function alleles in the genes , akt 1 and pdk 1 , encoding phosphoinositide dependent serine / threonine kinases . ^^^ Genetic epistasis analysis by RNAi showed that reproductive development in age 1 ( mg 109 ) ; akt 1 ( mg 247 ) animals was dependent on the presence of pdk 1 . ^^^ Similarly , reproductive development in age 1 ( mg 109 ) ; pdk 1 ( mg 261 ) animals was dependent on akt 1 . ^^^ However , reproductive development in age 1 ( mg 109 ) ; mg 227 animals required only akt 1 , and pdk 1 activity was dispensable in this background . ^^^ In contrast , akt 1 ( mg 247 ) and pdk 1 ( mg 261 ) did not affect lifespan or stress resistance , while both daf 16 alleles fully suppressed these phenotypes . ^^^
Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
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Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
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Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
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Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
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Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
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Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
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Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
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Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
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Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
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Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
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Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
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Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
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Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
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Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
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Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
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Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
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Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
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Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
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Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
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Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
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Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
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Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
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Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
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Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
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Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
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Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
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Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
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Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
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Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
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Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
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Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
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Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
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Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
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Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
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Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
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Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
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Interacting proteins: O15530 and P31749	Pubmed	SVM Score :0.0
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