G PROTEIN–COUPLED RECEPTOR KINASES

G protein-coupled receptor kinases.

G protein-coupled receptor kinases (GRKs) constitute a family of six mammalian serine/threonine protein kinases that phosphorylate agonist-bound, or activated, G protein-coupled receptors (GPCRs) as their primary substrates. GRK-mediated receptor phosphorylation rapidly initiates profound impairment of receptor signaling, or desensitization. This review focuses on the regulation of GRK activity...

Toxicology G Protein - Coupled Receptor Kinases

The importance of G protein-coupled receptor (GPCR) kinases (GRKs) as regulators of GPCR signaling has been widely recognized. In humans, GRKs constitute a family of seven protein kinases involved in the phosphorylation and desensitization of agonist-activated GPCRs in many physiological processes. The GPCR desensitization process is initiated by GRKs, but involves several subsequent steps incl...

A direct and functional interaction between the trimeric G protein Go and Rab5 in G proteincoupled receptor signaling

Peptide inhibitors of G protein-coupled receptor kinases.

G protein-coupled receptor kinases (GRKs) are regulatory enzymes involved in the modulation of seven-transmembrane-helix receptors. In order to develop specific inhibitors for these kinases, we synthesized and investigated peptide inhibitors derived from the sequence of the first intracellular loop of the beta2-adrenergic receptor. Introduction of changes in the sequence and truncation of N- an...

Molecular basis for activation of G protein-coupled receptor kinases.

G protein-coupled receptor (GPCR) kinases (GRKs) selectively recognize and are allosterically regulated by activated GPCRs, but the molecular basis for this interaction is not understood. Herein, we report crystal structures of GRK6 in which regions known to be critical for receptor phosphorylation have coalesced to stabilize the kinase domain in a closed state and to form a likely receptor doc...