E3B1, a human homologue of the mouse gene product Abi-1, sensitizes activation of Rap1 in response to epidermal growth factor
- Institute of Biomolecular Chemistry, Chemical Research Centre, Hungarian Academy of Sciences, Pusztaszeri Street 59-67, 1025 Budapest (Hungary)
- Experimental Pathology, Department of Laboratory Medicine, Lund University, Malmoe University Hospital, Entrance 78, SE-205 02 Malmoe (Sweden)
- Experimental Pathology, Department of Laboratory Medicine, Lund University, Malmoe University Hospital, Entrance 78, SE-205 02 Malmoe (Sweden) and Centre for Cancer Research and Cell Biology, Queen's University Belfast, Whitla Medical Building, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland (United Kingdom)
E3B1, a human homologue of the mouse gene product Abi-1, has been implicated in growth-factor-mediated regulation of the small GTPases p21{sup Ras} and Rac. E3b1 is a regulator of Rac because it can form a complex with Sos-1 and eps8, and such a Sos-1-e3B1-eps8 complex serves as a guanine nucleotide exchange factor for Rac. In the present study, we found that overexpression of e3B1 in NIH3T3/EGFR cells sensitized EGF-induced activation of Rac1, whereas it had no impact on EGF-induced activation of p21{sup Ras}. Remarkably, we found that EGF-induced activation of the p21{sup Ras}-related GTPase Rap1 was also sensitized in NIH3T3/EGFR-e3B1 cells. Thus, in NIH3T3/EGFR-e3B1 cells, maximal EGF-induced activation of Rap1 occurs with a dose of EGF much lower than in NIH3T3/EGFR cells. We also report that overexpression of e3B1 in NIH3T3/EGFR cells renders EGF-induced activation of Rap1 completely dependent on Src tyrosine kinases but not on c-Abl. However, EGF-induced tyrosine phosphorylation of the Rap GEF C3G occurred regardless of whether e3B1 was overexpressed or not, and this did not involve Src tyrosine kinases. Accordingly, we propose that overexpression of e3B1 in NIH3T3/EGFR cells leads to mobilization of Src tyrosine kinases that participate in EGF-induced activation of Rap1 and inhibition of cell proliferation.
- OSTI ID:
- 20717680
- Journal Information:
- Experimental Cell Research, Vol. 310, Issue 2; Other Information: DOI: 10.1016/j.yexcr.2005.08.010; PII: S0014-4827(05)00388-5; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
- Country of Publication:
- United States
- Language:
- English
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