Vav GEFs are required for beta2 integrin-dependent functions of neutrophils
| Autor: | Sheri L. Moores, Bin Zhang, M. Angelica Martinez Gakidis, Tanya N. Mayadas, Joan S. Brugge, Wojciech Swat, Xavier Cullere, Timothy S. Olson, Klaus Ley, Julie L. Wilsbacher |
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| Rok vydání: | 2004 |
| Předmět: |
rho GTP-Binding Proteins
VAV1 RHOA Neutrophils Integrin Cell Cycle Proteins Article 03 medical and health sciences Mice 0302 clinical medicine Phagocytosis Proto-Oncogene Proteins Cell Adhesion integrins cell adhesion Rho GTPases chemotaxis phagocytosis Animals Guanine Nucleotide Exchange Factors Cell adhesion Proto-Oncogene Proteins c-vav Paxillin Research Articles 030304 developmental biology Mice Knockout Oncogene Proteins 0303 health sciences biology Cell Biology Cell biology Chemotaxis Leukocyte CD18 Antigens Cancer research biology.protein Guanine nucleotide exchange factor Endothelium Vascular Signal transduction 030215 immunology Signal Transduction |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 0021-9525 |
| Popis: | Integrin regulation of neutrophils is essential for appropriate adhesion and transmigration into tissues. Vav proteins are Rho family guanine nucleotide exchange factors that become tyrosine phosphorylated in response to adhesion. Using Vav1/Vav3-deficient neutrophils (Vav1/3ko), we show that Vav proteins are required for multiple β2 integrin-dependent functions, including sustained adhesion, spreading, and complement-mediated phagocytosis. These defects are not attributable to a lack of initial β2 activation as Vav1/3ko neutrophils undergo chemoattractant-induced arrest on intercellular adhesion molecule-1 under flow. Accordingly, in vivo, Vav1/3ko leukocytes arrest on venular endothelium yet are unable to sustain adherence. Thus, Vav proteins are specifically required for stable adhesion. β2-induced activation of Cdc42, Rac1, and RhoA is defective in Vav1/3ko neutrophils, and phosphorylation of Pyk2, paxillin, and Akt is also significantly reduced. In contrast, Vav proteins are largely dispensable for G protein-coupled receptor–induced signaling events and chemotaxis. Thus, Vav proteins play an essential role coupling β2 to Rho GTPases and regulating multiple integrin-induced events important in leukocyte adhesion and phagocytosis. |
| Databáze: | OpenAIRE |
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