Regulation of tyrosine kinase activation and granule release through β-arrestin by CXCR1

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 CXCR1 was found to stimulate rapid formation of β-arrestin complexes with Hck or c-Fgr. Formation of β-arrestin–Hck complexes led to Hck activation and trafficking of the complexes to granule-rich regions. Granulocytes expressing a dominant-negative β-arrestin–mutant did not release granules or activate tyrosine kinases after IL-8 stimulation. Thus, β-arrestins regulate chemokine-induced granule exocytosis, indicating a broader role for β-arrestins in the regulation of cellular functions than was previously suspected.

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