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

Veronika Jenei, Tommy Andersson, J. Jakus, Karim Dib

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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 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.

Original languageEnglish
Pages (from-to)463-473
Number of pages11
JournalExperimental Cell Research
Volume310
Issue number2
DOIs
Publication statusPublished - Nov 1 2005

Fingerprint

Epidermal Growth Factor
Genes
src-Family Kinases
Proto-Oncogene Proteins p21(ras)
Guanine Nucleotide Exchange Factors
Monomeric GTP-Binding Proteins
GTP Phosphohydrolases
Tyrosine
Intercellular Signaling Peptides and Proteins
Phosphorylation
Cell Proliferation

Keywords

  • C3G
  • E3B1
  • EGF receptor
  • Rac
  • Rap1
  • Src tyrosine kinase

ASJC Scopus subject areas

  • Cell Biology

Cite this

E3B1, a human homologue of the mouse gene product Abi-1, sensitizes activation of Rap1 in response to epidermal growth factor. / Jenei, Veronika; Andersson, Tommy; Jakus, J.; Dib, Karim.

In: Experimental Cell Research, Vol. 310, No. 2, 01.11.2005, p. 463-473.

Research output: Contribution to journalArticle

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