E3B1, a human homologue of the mouse gene product Abi-1, sensitizes activation of Rap1 in response to epidermal growth factor

E3B1, a human homologue of the mouse gene product Abi-1, has been implicated in growth-factor-mediated regulation of the small GTPases p21(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(Ras). Remarkably, we found that EGF-induced activation of the p21(Ras)-related GTPase Rapt 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 Rapt 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.

Andersson, TommyLund University,Lunds universitet,Experimentell patologi, Malmö,Forskargrupper vid Lunds universitet,Experimental Pathology, Malmö,Lund University Research Groups(Swepub:lu)expp-tan (author)
Jakus, J (author)
Dib, KarimLund University,Lunds universitet,Experimentell patologi, Malmö,Forskargrupper vid Lunds universitet,Experimental Pathology, Malmö,Lund University Research Groups(Swepub:lu)expp-kdi (author)
Experimentell patologi, MalmöForskargrupper vid Lunds universitet (creator_code:org_t)

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

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