NDLI: Vav GEFs are required for β2 integrin-dependent functions of neutrophils

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Vav GEFs are required for β2 integrin-dependent functions of neutrophils

Content Provider	Semantic Scholar
Author	Gakidis, M. Angelica Martinez Cullere, Xavier Olson, Timothy Wilsbacher, Julie L. Zhang, Bin Moores, Sheri L. Ley, Klaus Swat, Wojciech Mayadas, Tanya Norton Brugge, Joan S.
Copyright Year	2004
Abstract	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 beta2 integrin-dependent functions, including sustained adhesion, spreading, and complement-mediated phagocytosis. These defects are not attributable to a lack of initial beta2 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. beta2-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 beta2 to Rho GTPases and regulating multiple integrin-induced events important in leukocyte adhesion and phagocytosis.
Starting Page	273
Ending Page	282
Page Count	10
File Format	PDF HTM / HTML
PubMed reference number	15249579
Volume Number	166
Journal	The Journal of cell biology
Alternate Webpage(s)	https://digitalcommons.wustl.edu/cgi/viewcontent.cgi?article=1583&context=open_access_pubs&httpsredir=1&referer=
Alternate Webpage(s)	http://ley-lab.liai.org/publications/228.pdf
Alternate Webpage(s)	http://jcb.rupress.org/content/jcb/166/2/273.full.pdf
Alternate Webpage(s)	http://digitalcommons.wustl.edu/cgi/viewcontent.cgi?article=1583&context=open_access_pubs
Alternate Webpage(s)	http://jcb.rupress.org/content/jcb/166/2/273.full.pdf?with-ds=yes
Language	English
Access Restriction	Open
Subject Keyword	Body tissue CD18 Antigens Chemotactic Factors Chemotaxis Complement System Proteins Guanine Nucleotide Exchange Factors Guanine Nucleotides Guanosine Triphosphate Phosphohydrolases Integrins Leukocytes PXN gene Phagocytosis Proto-Oncogene Proteins c-akt Tyrosine leukocyte cell-cell adhesion proto-oncogene protein vav rho Guanine Nucleotide Dissociation Inhibitor beta
Content Type	Text
Resource Type	Article

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