| Interacting proteins: Q92574 and P31749 |
Pubmed |
SVM Score :0.0 |
| We further demonstrate that Akt / PKB associates with hamartin tuberin complexes , promoting phosphorylation of tuberin and increased degradation of hamartin tuberin complexes . ^^^ Our results indicate that tuberin is a direct physiological substrate of Akt and that phosphorylation of tuberin by PI3K / Akt is a major mechanism controlling hamartin tuberin function . . ^^^ |
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| Interacting proteins: Q92574 and P31749 |
Pubmed |
SVM Score :0.0 |
| RECENT FINDINGS : These have been found in two major areas : genetic studies in Drosophila followed by studies in mammalian systems have identified the components of the Tuberous Sclerosis protein complex , a heterodimer of the proteins Hamartin and Tuberin , as inhibitors of TOR signaling , and as the major targets by which the insulin / IGF 1 signal transduction pathway , through the protein kinase PKB , and the energy status of the cell , through the AMP activated protein kinase , regulate the TOR signaling . ^^^ |
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| Interacting proteins: Q92574 and P31749 |
Pubmed |
SVM Score :0.0 |
| The complex of AS 250 with KIAA 1219 is notably similar to the important regulatory complex of the protein tuberin with hamartin ( the tuberous sclerosis complex ) , in the size of its subunits , the location of the GAP domain , and its phosphorylation by Akt . ^^^ |
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| Interacting proteins: Q92574 and P31749 |
Pubmed |
SVM Score :0.0 |
| Thus , tuberin bound by 14 3 3 in response to AKT phosphorylation is sequestered away from its membrane bound activation partner ( hamartin ) and its target GTPase ( Rheb ) to relieve the growth inhibitory effects of this tumor suppressor . . ^^^ |
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| Interacting proteins: Q92574 and P31749 |
Pubmed |
SVM Score :0.0 |
| Since phosphorylation of Bad occurred at serine 136 , the target of the serine / threonine kinase Akt , the effect of LAM on Akt kinase activity was tested . ^^^ Man LAM could activate Akt as evidenced from phosphorylation of Akt at Thr ( 308 ) and by the phosphorylation of the exogenous substrate histone 2B . ^^^ The phosphorylation of Bad by man LAM was abrogated in cells transfected with a kinase dead mutant of Akt . ^^^ These results establish that LAM mediated Bad phosphorylation occurs in a PI 3K / Akt dependent manner . ^^^ |
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| Interacting proteins: Q92574 and P31749 |
Pubmed |
SVM Score :0.0 |
| Accordingly , T47D cells grown on LAM had the greatest increase in ErbB 2 activation , PI3K activity , and phosphorylation of Akt . ^^^ |
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| Interacting proteins: Q92574 and P31749 |
Pubmed |
SVM Score :0.0 |
| Akt activity was unchanged in LAM cells . ^^^ |
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| Interacting proteins: Q92574 and P31749 |
Pubmed |
SVM Score :0.0 |
| Further genetic analyses suggest that the TSC genes act in a parallel pathway that converges on the insulin pathway downstream from Akt . ^^^ |
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| Interacting proteins: Q92574 and P31749 |
Pubmed |
SVM Score :0.0 |
| TSC 2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling . ^^^ Furthermore , TSC 2 is directly phosphorylated by Akt , which is involved in stimulating cell growth and is activated by growth stimulating signals , such as insulin . ^^^ TSC 2 is inactivated by Akt dependent phosphorylation , which destabilizes TSC 2 and disrupts its interaction with TSC 1 . ^^^ |
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| Interacting proteins: Q92574 and P31749 |
Pubmed |
SVM Score :0.0 |
| Akt regulates growth by directly phosphorylating Tsc 2 . ^^^ Here , we report that Drosophila melanogaster Akt / PKB stimulates growth by phosphorylating the tuberous sclerosis complex 2 ( Tsc 2 ) tumour suppressor and inhibiting formation of a Tsc 1 Tsc2 complex . ^^^ We show that Akt / PKB directly phosphorylates Drosophila Tsc 2 in vitro at the conserved residues , Ser 924 and Thr 1518 . ^^^ Mutation of these sites renders Tsc 2 insensitive to Akt / PKB signalling , increasing the stability of the Tsc 1 Tsc2 complex within the cell . ^^^ Stimulating Akt / PKB signalling in vivo markedly increases cell growth / size , disrupts the Tsc 1 Tsc2 complex and disturbs the distinct subcellular localization of Tsc 1 and Tsc 2 . ^^^ |
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| Interacting proteins: Q92574 and P31749 |
Pubmed |
SVM Score :0.0 |
| On growth factor stimulation , tuberin , the TSC 2 protein , is phosphorylated by Akt , thereby releasing its inhibitory effects on p70S6K . ^^^ |
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| Interacting proteins: Q92574 and P31749 |
Pubmed |
SVM Score :0.0 |
| TSC 2 , or tuberin , is the product of the tuberous sclerosis tumor suppressor gene TSC 2 and acts downstream of the phosphatidylinositol 3 kinase Akt signaling pathway to negatively regulate cellular growth . ^^^ Association between 14 3 3beta and TSC 2 requires phosphorylation of TSC 2 at a unique residue that is not a known Akt phosphorylation site . ^^^ |
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| Interacting proteins: Q92574 and P31749 |
Pubmed |
SVM Score :0.0 |
| Using genetic and biochemical methods , we have shown that Tsc 1 and Tsc 2 function in the insulin / phosphoinositide 3 kinase ( PI3K ) / Akt pathway . ^^^ We have shown that Akt regulates the Tsc 1 Tsc2 complex by directly phosphorylating Tsc 2 . ^^^ We have shown further that S 6 kinase ( S6K ) is a downstream component of the PI3K / Akt / TSC pathway and reduction of S6K activity can block TSC defects . ^^^ |
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| Interacting proteins: Q92574 and P31749 |
Pubmed |
SVM Score :0.0 |
| During mitogenic sufficiency , the phosphoinositide 3 kinase ( PI3K ) / Akt pathway phosphorylates tuberin on Ser 939 and Thr 1462 that inhibits the tumor suppressor function of the TSC complex . ^^^ |
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| Interacting proteins: Q92574 and P31749 |
Pubmed |
SVM Score :0.0 |
| There is a marked reduction in Akt activation in Tsc 2 ( / ) TP 53 ( / ) and Tsc 1 ( / ) cells in response to serum and PDGF , along with a reduction in cell ruffling . ^^^ PDGFRalpha and PDGFRbeta expression is markedly reduced in both the cell lines and Tsc mouse renal cystadenomas , and ectopic expression of PDGFRbeta in Tsc 2 null cells restores Akt phosphorylation in response to serum , PDGF , EGF , and insulin . ^^^ This activation of mTOR along with downregulation of PDGFR PI3K Akt signaling in cells lacking Tsc 1 or Tsc 2 may explain why these genes are rarely involved in human cancer . ^^^ |
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| Interacting proteins: Q92574 and P31749 |
Pubmed |
SVM Score :0.0 |
| Together , genetic and biochemical analysis places Scylla / Charybdis downstream of PKB and upstream of TSC . ^^^ |
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| Interacting proteins: Q92574 and P31749 |
Pubmed |
SVM Score :0.0 |
| AKT activation in human glioblastomas enhances proliferation via TSC 2 and S 6 kinase signaling . ^^^ Current models suggest that AKT acts directly , or indirectly via the TSC complex , to activate the mammalian target of rapamycin ( mTOR ) as the main downstream mediator of AKT signaling . mTOR activation results in subsequent activation of S6K and STAT 3 , as well as suppression ( i . e . , phosphorylation ) of 4E BP 1 , leading to cell cycle progression and inhibition of apoptosis . ^^^ Within individual tumors , increased expression levels of p TSC 2 , p mTOR , p 4E BP 1 , p S6K , p S 6 , and p STAT 3 were found in regions defined by elevated AKT activation . ^^^ However , only TSC 2 , S6K , and S 6 activation levels correlated significantly with AKT activation and clustered together in multidimensional scaling analyses . ^^^ These findings provide the first in vivo evidence for a close correlation between AKT and TSC 2 phosphorylation levels in glioblastoma . ^^^ |
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| Interacting proteins: Q92574 and P31749 |
Pubmed |
SVM Score :0.0 |
| Studies initiated in Drosophila have identified a role for the Tsc 1 and Tsc 2 genes in the regulation of cell and organ size , and genetic interaction studies have placed them in the PI3K Akt mTOR S6K pathway . ^^^ |
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| Interacting proteins: Q92574 and P31749 |
Pubmed |
SVM Score :0.0 |
| The signaling pathway downstream of Akt leading to mTOR involves the protein products of the genes mutated in tuberous sclerosis , TSC 1 and TSC 2 , and the small guanosine triphosphatase , Rheb . ^^^ |
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| Interacting proteins: Q92574 and P31749 |
Pubmed |
SVM Score :0.0 |
| Downstream of PI3K , the survival kinase , Akt , is completely refractory to activation by IRS dependent growth factor pathways such as insulin or IGF 1 in TSC 1 or TSC 2 deficient cells but not to activation by IRS independent pathways such as those utilized by PDGF . ^^^ |
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| Interacting proteins: Q92574 and P31749 |
Pubmed |
SVM Score :0.0 |
| The mTOR signaling network contains a number of tumor suppressor genes including PTEN , LKB 1 , TSC 1 , and TSC 2 , and a number of proto oncogenes including PI3K , Akt , and eIF4E , and mTOR signaling is constitutively activated in many tumor types . ^^^ |
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| Interacting proteins: Q92574 and P31749 |
Pubmed |
SVM Score :0.0 |
| PKB also phosphorylates the TSC 1 ( tuberous sclerosis complex 1 ) TSC 2 complex to relieve its inhibitory action on the mTOR ( mammalian target of rapamycin ) . ^^^ |
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| Interacting proteins: Q92574 and P31749 |
Pubmed |
SVM Score :0.0 |
| The AMPK signalling network contains a number of tumour suppressor genes including LKB 1 , p 53 , TSC 1 and TSC 2 , and overcomes growth factor signalling from a variety of stimuli ( via growth factors and by abnormal regulation of cellular proto oncogenes including PI3K , Akt and ERK ) . ^^^ |
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| Interacting proteins: Q92574 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q92574 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q92574 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q92574 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q92574 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q92574 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q92574 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q92574 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q92574 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q92574 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q92574 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q92574 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q92574 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q92574 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q92574 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q92574 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q92574 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q92574 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
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