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

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Author

Summary, in English

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.

Publishing year

2001

Language

English

Pages

6311-6322

Publication/Series

Journal of Immunology

Volume

166

Issue

10

Document type

Journal article

Publisher

American Association of Immunologists

Topic

  • Immunology in the medical area

Status

Published

Research group

  • Experimental Pathology, Malmö

ISBN/ISSN/Other

  • ISSN: 1550-6606