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Publication : Inhibition of beta 2 integrin receptor and Syk kinase signaling in monocytes by the Src family kinase Fgr.

First Author  Vines CM Year  2001
Journal  Immunity Volume  15
Issue  4 Pages  507-19
PubMed ID  11672534 Mgi Jnum  J:110529
Mgi Id  MGI:3640451 Doi  10.1016/s1074-7613(01)00221-7
Citation  Vines CM, et al. (2001) Inhibition of beta 2 integrin receptor and Syk kinase signaling in monocytes by the Src family kinase Fgr. Immunity 15(4):507-19
abstractText  While beta 2 integrin ligand-receptor recognition interactions are well characterized, less is known about how these events trigger signal transduction cascades to regulate the transition from tethering to firm adhesion, spreading, and transendothelial migration. We have identified critical positive and negative regulatory components of this cascade in monocytes. Whereas the Syk tyrosine kinase is essential for beta 2 integrin signaling and cell spreading, the Src family kinase Fgr is a negative regulator of this pathway. Fgr selectively inhibits beta 2 but not beta 1 integrin signaling and Syk kinase function via a direct association between the Fgr SH2 domain and Syk tyrosine Y342. The inhibitory effects of Fgr are independent of its kinase activity, are dose dependent, and can be overcome by chemokines and inflammatory mediators.
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