The function of p120^<cbl>, the product of c-cbl protooncogene

2001 Fiscal Year Final Research Report Summary

• Project/Area Number: 11670443
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 内科学一般
• Research Institution: The University of Tokyo
• Principal Investigator: OTA Yasuo Faculty of Medicine, The University of Tokyo, Lecturer, 医学部・附属病院, 助手 (80292936)
• Project Period (FY): 1999 – 2000
• Keywords: Cbl / Grb2 / EGF / MAPK

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>.