A surface of the kinase domain critical for the allosteric activation of G protein-coupled receptor kinases.

ABSTRACT: G protein-coupled receptor (GPCR) kinases (GRKs) phosphorylate activated GPCRs and initiate their desensitization. Many prior studies suggest that activated GPCRs dock to an allosteric site on the GRKs and thereby stimulate kinase activity. The extreme N-terminal region of GRKs is clearly involved in this process, but its role is not understood. Using our recent structure of bovine GRK1 as a guide, we generated mutants of solvent-exposed residues in the GRK1 kinase domain that are conserved among GRKs but not in the extended protein kinase A, G, and C family and evaluated their catalytic activity. Mutation of select residues in strands beta1 and beta3 of the kinase small lobe, alphaD of the kinase large lobe, and the protein kinase A, G, and C kinase C-tail greatly impaired receptor phosph

SUBMITTER: Huang CC 

PROVIDER: S-EPMC2719358 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature