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 p21Ras 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 p21Ras. Remarkably, we found that EGF-induced activation of the p21Ras-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.
Jenei
Veronika
V
Institute of Biomolecular Chemistry, Chemical Research Centre, Hungarian Academy of Sciences, Pusztaszeri Street 59-67, 1025 Budapest, Hungary.
Andersson
Tommy
T
Jakus
Judit
J
Dib
Karim
K
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D003598:Cytoskeletal Proteins; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D020735:Guanine Nucleotide-Releasing Factor 2 / Q000378:metabolism; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction; D015533:Transcriptional Activation; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*; D020827:rap1 GTP-Binding Proteins / Q000378:metabolism*; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
C513733:ABI1 protein, human; C513734:Abi1 protein, mouse; D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D020735:Guanine Nucleotide-Releasing Factor 2; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D019061:src-Family Kinases; D020830:rac1 GTP-Binding Protein; D020827:rap1 GTP-Binding Proteins