GRK5
Serine/threonine kinase that phosphorylates preferentially the activated forms of a variety of G-protein-coupled receptors (GPCRs). Such receptor phosphorylation initiates beta-arrestin-mediated receptor desensitization, internalization, and signaling events leading to their down-regulation. Phosphorylates a variety of GPCRs, including adrenergic receptors, muscarinic acetylcholine receptors (more specifically Gi-coupled M2/M4 subtypes), dopamine receptors and opioid receptors. In addition to GPCRs, also phosphorylates various substrates: Hsc70-interacting protein/ST13, TP53/p53, HDAC5, and arrestin-1/ARRB1. Phosphorylation of ARRB1 by GRK5 inhibits G-protein independent MAPK1/MAPK3 signaling downstream of 5HT4-receptors. Phosphorylation of HDAC5, a repressor of myocyte enhancer factor 2 (MEF2) leading to nuclear export of HDAC5 and allowing MEF2-mediated transcription. Phosphorylation of TP53/p53, a crucial tumor suppressor, inhibits TP53/p53-mediated apoptosis. Phosphorylation of ST13 regulates internalization of the chemokine receptor. Phosphorylates rhodopsin (RHO) (in vitro) and a non G-protein-coupled receptor, LRP6 during Wnt signaling (in vitro). Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. GPRK subfamily. Highest levels in heart, placenta, lung Note: This description may include information from UniProtKB.
Protein type: AGC group; EC 2.7.11.16; GRK family; GRK subfamily; Kinase, protein; Protein kinase, AGC; Protein kinase, Ser/Thr (non-receptor)
Molecular Function: ATP binding; beta-adrenergic receptor kinase activity; G protein-coupled receptor kinase activity; kinase activity; lipid binding; nucleotide binding; protein binding; protein kinase activity; protein serine/threonine kinase activity; transferase activity
Biological Process: apoptotic process; desensitization of G protein-coupled receptor signaling pathway; fat cell differentiation; negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway; negative regulation of apoptotic process; phosphorylation; positive regulation of cell population proliferation; protein autophosphorylation; protein phosphorylation; regulation of cell cycle; regulation of G protein-coupled receptor signaling pathway; regulation of signal transduction; signal transduction; tachykinin receptor signaling pathway; Wnt signaling pathway
