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Role of p190RhoGAP in beta(2) integrin regulation of RhoA in human neutrophils

Dib, Karim LU ; Melander, Fredrik and Andersson, Tommy LU (2001) In Journal of Immunology 166(10). p.6311-6322
Abstract
We found that engagement of beta (2) integrins on human neutrophils induced activation of RhoA, as indicated by the increased ratio of GTP:GTP + GDP recovered on RhoA and translocation of RhoA to a membrane fraction. The clustering of beta (2) integrins also induced a time-dependent increase in GDP bound to RhoA, which correlated with beta (2) integrin-induced activation of p190RhoGAP. The activation of p190RhoGAP was completely blocked by [4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine] (PP1), a selective inhibitor of Src family tyrosine kinases. However, clustering of beta (2) integrins did not increase the basal tyrosine phosphorylation of p190RhoGAP, nor did it affect the amount of p120RasGAP bound to p190RhoGAP.... (More)
We found that engagement of beta (2) integrins on human neutrophils induced activation of RhoA, as indicated by the increased ratio of GTP:GTP + GDP recovered on RhoA and translocation of RhoA to a membrane fraction. The clustering of beta (2) integrins also induced a time-dependent increase in GDP bound to RhoA, which correlated with beta (2) integrin-induced activation of p190RhoGAP. The activation of p190RhoGAP was completely blocked by [4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine] (PP1), a selective inhibitor of Src family tyrosine kinases. However, clustering of beta (2) integrins did not increase the basal tyrosine phosphorylation of p190RhoGAP, nor did it affect the amount of p120RasGAP bound to p190RhoGAP. Instead, the beta (2) integrin-induced activation of p190RhoGAP was accompanied by increased tyrosine phosphorylation of a p190RhoGAP-associated protein, p120RasGAP, and accumulation of both p120RasGAP and p190RhoGAP in a membrane fraction. PP1 blocked the beta (2) integrin-induced phosphorylation of p120RasGAP, as well as the translocation of p190RhoGAP and p120RasGAP, but it did not affect the accumulation of RhoA in the membrane fraction. In agreement with the mentioned findings, PP1 also increased the GTP:GTP + GDP ratio recovered on RhoA immunoprecipitated from beta (2) integrin-stimulated cells. Thus, in neutrophils, beta (2) integrin-induced activation of p190RhoGAP requires a signal from a Src family tyrosine kinase, but it does not occur via the signaling pathway responsible for activation of RhoA. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Immunology
volume
166
issue
10
pages
6311 - 6322
publisher
American Association of Immunologists
external identifiers
  • wos:000170948500059
ISSN
1550-6606
language
English
LU publication?
yes
id
18081955-679d-4f8b-aa8b-27b69763024d (old id 1118940)
date added to LUP
2008-06-26 12:33:21
date last changed
2018-05-29 09:31:41
@article{18081955-679d-4f8b-aa8b-27b69763024d,
  abstract     = {We found that engagement of beta (2) integrins on human neutrophils induced activation of RhoA, as indicated by the increased ratio of GTP:GTP + GDP recovered on RhoA and translocation of RhoA to a membrane fraction. The clustering of beta (2) integrins also induced a time-dependent increase in GDP bound to RhoA, which correlated with beta (2) integrin-induced activation of p190RhoGAP. The activation of p190RhoGAP was completely blocked by [4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine] (PP1), a selective inhibitor of Src family tyrosine kinases. However, clustering of beta (2) integrins did not increase the basal tyrosine phosphorylation of p190RhoGAP, nor did it affect the amount of p120RasGAP bound to p190RhoGAP. Instead, the beta (2) integrin-induced activation of p190RhoGAP was accompanied by increased tyrosine phosphorylation of a p190RhoGAP-associated protein, p120RasGAP, and accumulation of both p120RasGAP and p190RhoGAP in a membrane fraction. PP1 blocked the beta (2) integrin-induced phosphorylation of p120RasGAP, as well as the translocation of p190RhoGAP and p120RasGAP, but it did not affect the accumulation of RhoA in the membrane fraction. In agreement with the mentioned findings, PP1 also increased the GTP:GTP + GDP ratio recovered on RhoA immunoprecipitated from beta (2) integrin-stimulated cells. Thus, in neutrophils, beta (2) integrin-induced activation of p190RhoGAP requires a signal from a Src family tyrosine kinase, but it does not occur via the signaling pathway responsible for activation of RhoA.},
  author       = {Dib, Karim and Melander, Fredrik and Andersson, Tommy},
  issn         = {1550-6606},
  language     = {eng},
  number       = {10},
  pages        = {6311--6322},
  publisher    = {American Association of Immunologists},
  series       = {Journal of Immunology},
  title        = {Role of p190RhoGAP in beta(2) integrin regulation of RhoA in human neutrophils},
  volume       = {166},
  year         = {2001},
}