Regulation of tyrosine kinase activation and granule release through beta-arrestin by CXCRI

  • Nat Immunol. 2000 Sep;1(3):227-33. doi: 10.1038/79767.
J Barlic  1 ,  J D Andrews ,  A A Kelvin ,  S E Bosinger ,  M E DeVries ,  L Xu ,  T Dobransky ,  R D Feldman ,  S S Ferguson ,  D J Kelvin
Affiliations
  • 1. Laboratory of Molecular Immunology and Inflammation, John P. Robarts Research Institute, 1400 Western Road, London, Ontario, Canada, N6G 2V4.
PMID: 10973280 DOI: 10.1038/79767
Abstract

Chemoattractant-stimulated granule release from neutrophils, basophils and eosinophils is critical for the innate immune response against infectious bacteria. Interleukin 8 (IL-8) activation of the Chemokine Receptor CXCRI was found to stimulate rapid formation of beta-arrestin complexes with HCK or c-Fgr. Formation of beta-arrestin-Hck complexes led to HCK activation and trafficking of the complexes to granule-rich regions. Granulocytes expressing a dominant-negative beta-arrestin-mutant did not release granules or activate tyrosine Kinases after IL-8 stimulation. Thus, beta-arrestins regulate chemokine-induced granule exocytosis, indicating a broader role for beta-arrestins in the regulation of cellular functions than was previously suspected.