References
Query Results -- Details
MGI Accession ID: MGI:3718272
J Number: J:123408
Other Accession IDs:
Title: P-selectin primes leukocyte integrin activation during inflammation.
Authors: Wang HB; Wang JT; Zhang L; Geng ZH; Xu WL; Xu T; Huo Y; Zhu X; Plow EF; Chen M; Geng JG
Journal: Nat Immunol
Volume: 8
Issue: 8
Date: 2007 Aug
Year: 2007
Pages: 882-892
Review Status: Peer Reviewed
Abstract:
Selectins mediate leukocyte rolling and prime leukocytes for integrin-mediated leukocyte adhesion. However, neither the in vivo importance of nor the signaling pathway by which selectin-mediated integrin activation occurs has been determined. We report here that P-selectin-deficient mice manifested impaired leukocyte adhesion, which was 'rescued' by soluble P-selectin. Mechanistically, the cytoplasmic domain of P-selectin glycoprotein ligand 1 formed a constitutive complex with Nef-associated factor 1. After binding of P-selectin, Src kinases phosphorylated Nef-associated factor 1, which recruited the phosphoinositide-3-OH kinase p85-p110delta heterodimer and resulted in activation of leukocyte integrins. Inhibition of this signal-transduction pathway diminished the adhesion of leukocytes to capillary venules and suppressed peritoneal infiltration of leukocytes. Our data demonstrate the functional importance of this newly identified signaling pathway mediated by P-selectin glycoprotein ligand 1.
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