| Interacting proteins: O14757 and P31749 |
Pubmed |
SVM Score :0.0 |
| Preliminary data show that PKB phosphorylates the Chk 1 polypeptide in vitro on serine 280 . ^^^ |
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| Interacting proteins: O14757 and P31749 |
Pubmed |
SVM Score :0.0 |
| This article will focus on two emerging and less explored protein serine / threonine kinase targets : PKB / Akt and checkpoint kinase 1 ( Chk 1 ) . ^^^ |
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| Interacting proteins: O14757 and P31749 |
Pubmed |
SVM Score :0.0 |
| Inhibition of Chk 1 by activated PKB / Akt . ^^^ We have shown recently that DNA damage effector kinase Chk 1 is phosphorylated in vitro by protein kinase B / Akt ( PKB / Akt ) on serine 280 . ^^^ Activation of Chk 1 by DNA damage in vivo is suppressed in presence of activated PKB . ^^^ In this study we show that Chk 1 is phosphorylated by PKB in vivo , and that increased phosphorylation by PKB on serine 280 correlates with impairment of Chk 1 activation by DNA damage . ^^^ The Chk 1 protein phosphorylated by PKB on serine 280 does not enter into protein complexes after replication arrest . ^^^ |
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| Interacting proteins: O14757 and P31749 |
Pubmed |
SVM Score :0.0 |
| Farnesyltransferase inhibitors interact synergistically with the Chk 1 inhibitor UCN 01 to induce apoptosis in human leukemia cells through interruption of both Akt and MEK / ERK pathways and activation of SEK1 / JNK . ^^^ |
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| Interacting proteins: O14757 and P31749 |
Pubmed |
SVM Score :0.0 |
| Hematopoietic cytokines enhance Chk 1 dependent G2 / M checkpoint activation by etoposide through the Akt / GSK3 pathway to inhibit apoptosis . ^^^ Furthermore , SB 216763 or LiCl , a specific inhibitor for the GSK 3 kinase inhibited by Akt , enhanced the Chk 1 phosphorylation and G2 / M arrest by etoposide . ^^^ These results indicate that hematopoietic cytokines protect etoposide treated cells from DNA damage induced apoptosis by promoting , through the PI3K / Akt / GSK3 signaling pathway , G2 / M checkpoint that is dependent on Chk 1 mediated inhibition of Cdc2 . . ^^^ |
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| Interacting proteins: O14757 and P31749 |
Pubmed |
SVM Score :0.0 |
| The checkpoint defect was traced to the ability of AKT to phosphorylate CHK 1 at serine 280 , since a nonphosphorylated mutant of CHK 1 ( S280A ) complemented the checkpoint defect and restored CDC25A degradation . ^^^ Primary breast carcinomas lacking PTEN expression and having elevated AKT phosphorylation had increased cytoplasmic CHK 1 and displayed aneuploidy ( p < 0 . 005 ) . ^^^ We conclude that loss of PTEN and subsequent activation of AKT impair CHK 1 through phosphorylation , ubiquitination , and reduced nuclear localization to promote genomic instability in tumor cells . . ^^^ |
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| Interacting proteins: O14757 and P31749 |
Pubmed |
SVM Score :0.0 |
| Akt mediated suppression of G 2 arrest was associated not with alterations in Chk 1 or p 38 activation but rather with suppression of Chk 2 activation and reduced recruitment of Chk 2 to sites of damage in chromatin . ^^^ Unlike bypass of the G 2 checkpoint induced by pharmacologic inhibitors of Chk 1 or p 38 , however , Akt induced bypass of G 2 arrest suppressed , rather than enhanced , temozolomide induced senescence and mitotic catastrophe . ^^^ |
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| Interacting proteins: O14757 and P31749 |
Pubmed |
SVM Score :0.0 |
| Moreover , we show that the site of CHK 1 ubiquitination ( K 274 ) is near the site of AKT phosphorylation ( S 280 ) . ^^^ |
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| Interacting proteins: O14757 and P31749 |
Pubmed |
SVM Score :0.0 |
| Chk 1 and Akt signaling facilitate survival of cells treated with nucleoside analogues . ^^^ Activation of Chk 1 in response to cytarabine ( ara C ) induced an S phase checkpoint characterized by the inhibition of Cdk 2 , cell cycle arrest , no change in constitutively active Akt , or low stress kinase signaling in ML 1 cells . ^^^ However , inhibition of Chk 1 by UCN 01 in S phase arrested cells resulted in an abrogation of the checkpoint , inhibition of Akt , activation of JNK , and a rapid induction of apoptosis . ^^^ Thus , use of UCN 01 in combination with ara C decreases Chk 1 phosphorylation , inhibits the Akt survival pathway , and activates JNK during the course of therapy , offering a rationale for the cytotoxic action of this combination during AML treatment . . ^^^ |
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| Interacting proteins: O14757 and P31749 |
Pubmed |
SVM Score :0.0 |
| Lovastatin affected various IR induced stress responses in HUVEC : It attenuated the increase in p53 / p21 protein level and impaired the activation of nuclear factor kappaB , Chk 1 , and Akt kinase but did not inhibit extracellular signal regulated kinase activation . ^^^ |
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| Interacting proteins: O14757 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: O14757 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
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