title: Regulation of tyrosine kinase activation and granule release through beta-arrestin by CXCRI.
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.
authors.affiliation: Laboratory of Molecular Immunology and Inflammation, John P. Robarts Research Institute, 1400 Western Road, London, Ontario, Canada, N6G 2V4.
authors.forename: J
authors.initials: J
authors.lastname: Barlic
authors.forename: J D
authors.initials: JD
authors.lastname: Andrews
authors.forename: A A
authors.initials: AA
authors.lastname: Kelvin
authors.forename: S E
authors.initials: SE
authors.lastname: Bosinger
authors.forename: M E
authors.initials: ME
authors.lastname: DeVries
authors.forename: L
authors.initials: L
authors.lastname: Xu
authors.forename: T
authors.initials: T
authors.lastname: Dobransky
authors.forename: R D
authors.initials: RD
authors.lastname: Feldman
authors.forename: S S
authors.initials: SS
authors.lastname: Ferguson
authors.forename: D J
authors.initials: DJ
authors.lastname: Kelvin
mesh_terms: D000595:Amino Acid Sequence; D019390:Arrestins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015550:Cell Degranulation; D003594:Cytoplasmic Granules / Q000378:metabolism*; D004789:Enzyme Activation; D006098:Granulocytes / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000494:pharmacology; D008969:Molecular Sequence Data; D011505:Protein-Tyrosine Kinases / Q000378:metabolism* / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000502:physiology; D051572:Proto-Oncogene Proteins c-hck; D023062:Receptors, Interleukin-8A / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014162:Transfection; D000071557:beta-Arrestins; D019061:src-Family Kinases
chemical_list: D019390:Arrestins; D016209:Interleukin-8; D011518:Proto-Oncogene Proteins; D023062:Receptors, Interleukin-8A; D000071557:beta-Arrestins; D011505:Protein-Tyrosine Kinases; C496631:HCK protein, human; D051572:Proto-Oncogene Proteins c-hck; C053102:proto-oncogene proteins c-fgr; D019061:src-Family Kinases