Regulation of tyrosine kinase activation and granule release through beta-arrestin by CXCRI.
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.
Barlic
J
J
Laboratory of Molecular Immunology and Inflammation, John P. Robarts Research Institute, 1400 Western Road, London, Ontario, Canada, N6G 2V4.
Andrews
J D
JD
Kelvin
A A
AA
Bosinger
S E
SE
DeVries
M E
ME
Xu
L
L
Dobransky
T
T
Feldman
R D
RD
Ferguson
S S
SS
Kelvin
D J
DJ
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
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