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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Amino Acid Sequence
-
Arrestins / genetics
-
Arrestins / metabolism
-
Arrestins / physiology*
-
Cell Degranulation
-
Cytoplasmic Granules / metabolism*
-
Enzyme Activation
-
Granulocytes / immunology
-
Granulocytes / metabolism
-
Humans
-
Interleukin-8 / pharmacology
-
Molecular Sequence Data
-
Protein-Tyrosine Kinases / metabolism*
-
Protein-Tyrosine Kinases / physiology
-
Proto-Oncogene Proteins / metabolism
-
Proto-Oncogene Proteins / physiology
-
Proto-Oncogene Proteins c-hck
-
Receptors, Interleukin-8A / genetics
-
Receptors, Interleukin-8A / metabolism
-
Receptors, Interleukin-8A / physiology*
-
Transfection
-
beta-Arrestins
-
src-Family Kinases
Substances
-
Arrestins
-
Interleukin-8
-
Proto-Oncogene Proteins
-
Receptors, Interleukin-8A
-
beta-Arrestins
-
Protein-Tyrosine Kinases
-
HCK protein, human
-
Proto-Oncogene Proteins c-hck
-
proto-oncogene proteins c-fgr
-
src-Family Kinases