Inhibition of β2 integrin receptor and Syk kinase signaling in monocytes by the Src family kinase Fgr

Charlotte M. Vines, Jeffrey W. Potter, Yin Xu, Robert L. Geahlen, Patrick S. Costello, Victor L. Tybulewicz, Clifford A. Lowell, Peter W. Chang, Hattie D. Gresham, Cheryl L. Willman

Research output: Contribution to journalArticlepeer-review

Abstract

While β2 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 β2 integrin signaling and cell spreading, the Src family kinase Fgr is a negative regulator of this pathway. Fgr selectively inhibits β2 but not β1 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.

Original languageEnglish (US)
Pages (from-to)507-519
Number of pages13
JournalImmunity
Volume15
Issue number4
DOIs
StatePublished - 2001

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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