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

Immunity | Oct 23, 2001

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.

Pubmed ID: 11672534 RIS Download

Mesh terms: Animals | Antigens, CD18 | Cell Adhesion | Cell Line | Cell Size | Cells, Cultured | Chemokines | Enzyme Precursors | Intracellular Signaling Peptides and Proteins | Macrophages | Mice | Mice, Knockout | Monocytes | Protein-Tyrosine Kinases | Proto-Oncogene Proteins | Proto-Oncogene Proteins c-hck | Signal Transduction | Syk Kinase | Transfection | src Homology Domains | src-Family Kinases

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Associated grants

  • Agency: NIDDK NIH HHS, Id: DK43042
  • Agency: NIDDK NIH HHS, Id: DK50267
  • Agency: NHLBI NIH HHS, Id: HL54467

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