| Project/Area Number |
11670443
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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 |
内科学一般
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| Research Institution | The University of Tokyo |
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Principal Investigator |
OTA Yasuo Faculty of Medicine, The University of Tokyo, Lecturer, 医学部・附属病院, 助手 (80292936)
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| Co-Investigator(Kenkyū-buntansha) |
北沢 貴利 東京大学, 医学部・附属病院, 医員
人見 重美 東京大学, 医学部・附属病院, 助手 (40292916)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1999: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | Cbl / Grb2 / EGF / MAPK / EGF受容体 / 細胞内情報伝達 / プロトオンコジンCbl |
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| Research Abstract |
We tried to elucidate the function of p120^<cbl>, the product of the c-cbl protooncogene after EGF receptor stimulation. We generated several MDCK cell lines which stably express wild type p120^<cbl> or mutant p120^<cbl>. In this project we compared the signal transudation cascades after EGF stimulation in the p120^<cbl> stable transfectants.
p120^<cbl> is a prominent tyrosine-phosphorylated substrate in a wide variety of cells_-p120^<cbl> is one of several substrates that binds to Grb2 in vitro and in vivo through the amino-terminal SH3 domain of Grb2. Like Sosl, p120^<cbl> has a proline-rich region that includes likely motifs for binding to SH3 domains. However, p120^<cbl> and Sosl do not coimmunoprecipitate, suggesting that p120^<cbl>-Grb2 and Sosl-Grb2 are separate complexes.
The Grb2-p120^<cbl> interaction is mediated through the amino-terminal SH3 domain of Grb2 (N-SH3-Grb2), and we map the region of p120^<cbl> which interacts constitutively with Grb2. This region of p120^<cbl> was found to be between amino acids 543 and 548.
We also show that phosphorylation of MAPK is markedly prolonged after addition of EGF in cells which express the proline-rich (543-548) mutated p120^<cbl>.
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