1996 Fiscal Year Final Research Report Summary
Analysis of Oncogenesis by CRK, an Adaptor-type Oncogene
| Project/Area Number |
08670266
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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 |
Experimental pathology
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| Research Institution | Research Institute, International Medical Center of Japan |
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Principal Investigator |
MATSUDA Micheyuki Internatioal Medical Center of Japan, Researching Intsitute Department of Pathology, Director, 臨床病理研究部, 部長 (10199812)
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| Co-Investigator(Kenkyū-buntansha) |
NAGASHIMA Kazuo Hokkaido Unversity School of Medicine Department of Pathology, Professor, 医学部, 教授 (50010377)
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| Project Period (FY) |
1996 – 1998
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| Keywords | CRK / C3G / Rap1 / Epidermal growth factor / Nef |
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| Research Abstract |
We have analyzed the activation mechanism of C3G, the major downstream factor of Crk adaptor-type oncogene. C3G is a guanine-nucleotide exchange factor for Rap1. Expression of Crk activated C3G. Deletion of the amino-terminal region of C3G increased the guanine-nucleotide exchange reaction of Rap I mediated by C3G. This result indicated that the amino-terminal region of C3G functioned as a cis-acting negative regulatory element and that Crk repressed this negative regulation. Mutation analysis revealed that both the SH2 and SH3 domains of Crk was required for the activation of C3G. Moreover, we found that epidermal growth factor induced tyrosine phosphorylation of Crk and that this phosphorylation triggered the dissociation of Crk from C3G. Thus, upon epidermal growth factor stimulation, C3G is recruited to the membrane by Crk and, there, dissociates from the tyrosine-phosphorylated Crk.
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Research Products
(6 results)
