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

Jenei, V; Andersson, Tommy LU ; Jakus, J and Dib, Karim LU (2005) In Experimental Cell Research 310(2). p.463-473
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 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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Src tyrosine kinase, Rap1, Rac, E3B1, EGF receptor, C3G
in
Experimental Cell Research
volume
310
issue
2
pages
463 - 473
publisher
Academic Press
external identifiers
  • pmid:16182283
  • wos:000232992900021
  • scopus:26844567358
ISSN
1090-2422
DOI
10.1016/j.yexcr.2005.08.010
language
English
LU publication?
yes
id
f956598e-3745-480c-b301-700c27a2cd42 (old id 214257)
date added to LUP
2007-08-10 14:00:43
date last changed
2017-01-01 05:16:01
@article{f956598e-3745-480c-b301-700c27a2cd42,
  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 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.},
  author       = {Jenei, V and Andersson, Tommy and Jakus, J and Dib, Karim},
  issn         = {1090-2422},
  keyword      = {Src tyrosine kinase,Rap1,Rac,E3B1,EGF receptor,C3G},
  language     = {eng},
  number       = {2},
  pages        = {463--473},
  publisher    = {Academic Press},
  series       = {Experimental Cell Research},
  title        = {E3B1, a human homologue of the mouse gene product Abi-1, sensitizes activation of Rap1 in response to epidermal growth factor},
  url          = {http://dx.doi.org/10.1016/j.yexcr.2005.08.010},
  volume       = {310},
  year         = {2005},
}