A study on the mechanism of PI3K/AKT pathway activation by v-Crk oncogene
| Project/Area Number |
13670308
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Virology
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| Research Institution | Osaka Bioscience Institute |
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Principal Investigator |
AKAGI Tsuyoshi Osaka Bioscience Institute, Director's Lab, Vice Head., 所長研究部, 研究副部長 (90184077)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2002: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2001: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Crk / PI3K / AKT / FAK / Src / SH2 / SH3 / Ras / v-CrK / P13K |
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| Research Abstract |
v-Crk, an oncogene product of avian sarcoma virus CT10, transforms chicken embryo fibroblasts (CEF) efficiently. We have recently reported that phosphatidylinositide 3-kinase(PI3K)/AKT pathway is constitutively activated and play a critical role in the oncogenic transformation of CEF by v-Crk. In this study, we investigated how v-Crk activates PI3K/AKT pathway and revealed the involvement of focal adhesion kinase (FAK) and H-Ras in this process. v-Crk induces phosphorylation of Tyr 397 residue in FAK through the activation of src-family tyrosine kinase(s), in which SH2 domain of v-Crk is responsible, and promotes the binding of N-terminal SH2 domain of PI3K p85 regulatory subunit to this site. v-Crk fails to activate PI3K/AKT pathway in FAK null cells. In addition, we found that v-Crk stimulates the interaction of H-Ras with Ras binding domain in PI3K p110 catalytic subunit, and that the expression of H-Ras or its guanine nucleotide exchange factor mSOS, which binds to SH3 domain of v-Crk, enhances the v-Crk-induced activation of AKT, while a doninant negative mutant of H-Ras almost completely suppresses this activation. Our data demonstrated that v-Crk activates PI3K/AKT pathway by promoting both the interaction of p85 with tyrosine phosphorylated FAK and the interaction of p110 with H-Ras.
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Report
(3 results)
Research Products
(8 results)
