Phospholipid-stimulated autophosphorylation activates the G protein-coupled receptor kinase GRK5.

Kunapuli P, Gurevich VV, Benovic JL
J Biol Chem. 1994 269 (14): 10209-12

PMID: 8144599

G protein-coupled receptor kinases (GRKs) play an important role in mediating agonist-specific desensitization of numerous G protein-coupled receptors. GRK5, a recently identified member of the GRK family, undergoes a rapid phospholipid-stimulated autophosphorylation to a stoichiometry of approximately 2 mol of phosphate/mol of GRK5. The ability of phospholipids to stimulate autophosphorylation is largely blocked by a glutathione S-transferase fusion protein containing the last 102 amino acids of GRK5 (amino acids 489-590), suggesting that this is a primary region involved in GRK5/phospholipid interaction. Phosphoamino acid determination and mutagenesis studies demonstrate that autophosphorylation of GRK5 occurs primarily at residues Ser-484 and Thr-485. Expression and characterization of a mutant GRK5 that does not autophosphorylate (S484A and T485A) reveals that the mutant has a approximately 15-20-fold reduced ability to phosphorylate the beta 2-adrenergic receptor and rhodopsin compared to wild type GRK5. These results suggest that phospholipid-stimulated autophosphorylation may represent a novel mechanism for membrane association and regulation of GRK5 activity.

MeSH Terms (14)

Amino Acid Sequence Animals Base Sequence Cells, Cultured Cricetinae DNA Primers G-Protein-Coupled Receptor Kinase 5 GTP-Binding Proteins Lepidoptera Molecular Sequence Data Phospholipids Phosphorylation Protein-Serine-Threonine Kinases Receptor Protein-Tyrosine Kinases

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