{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T09:23:50Z","timestamp":1791969830985,"version":"4.3.4"},"reference-count":53,"publisher":"Rockefeller University Press","issue":"10","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2008,9,29]]},"abstract":"<jats:p>E-selectin binding to P-selectin glycoprotein ligand-1 (PSGL-1) can activate the \u03b22 integrin lymphocyte function-associated antigen-1 by signaling through spleen tyrosine kinase (Syk). This signaling is independent of G\u03b1i-protein\u2013coupled receptors, results in slow rolling, and promotes neutrophil recruitment to sites of inflammation. However, the signaling pathways linking E-selectin engagement of PSGL-1 to Syk activation are unknown. To test the role of Src family kinases and immunoreceptor tyrosine-based activating motif (ITAM)\u2013containing adaptor proteins, we used different gene-deficient mice in flow chamber, intravital microscopy, and peritonitis studies. E-selectin\u2013mediated phosphorylation of Syk and slow rolling was abolished in neutrophils from fgr\u2212\/\u2212 or hck\u2212\/\u2212 lyn\u2212\/\u2212 fgr\u2212\/\u2212 mice. Neutrophils from Tyrobp\u2212\/\u2212 Fcrg\u2212\/\u2212 mice lacking both DAP12 and FcR\u03b3 were incapable of sustaining slow neutrophil rolling on E-selectin and intercellular adhesion molecule-1 and were unable to phosphorylate Syk and p38 MAPK. This defect was confirmed in vivo by using mixed chimeric mice. G\u03b1i-independent neutrophil recruitment into the inflamed peritoneal cavity was sharply suppressed in Tyrobp\u2212\/\u2212 Fcrg\u2212\/\u2212 mice. Our data demonstrate that an ITAM-dependent pathway involving the Src-family kinase Fgr and the ITAM-containing adaptor proteins DAP12 and FcR\u03b3 is involved in the initial signaling events downstream of PSGL-1 that are required to initiate neutrophil slow rolling.<\/jats:p>","DOI":"10.1084\/jem.20072660","type":"journal-article","created":{"date-parts":[[2008,9,15]],"date-time":"2008-09-15T21:09:38Z","timestamp":1221512978000},"page":"2339-2347","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":182,"title":["PSGL-1 engagement by E-selectin signals through Src kinase Fgr and ITAM adapters DAP12 and FcR\u03b3 to induce slow leukocyte rolling"],"prefix":"10.1084","volume":"205","author":[{"given":"Alexander","family":"Zarbock","sequence":"first","affiliation":[{"name":"1Robert M. 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