GRK5

This gene encodes a member of the guanine nucleotide-binding protein (G protein)-coupled receptor kinase subfamily of the Ser/Thr protein kinase family. The protein phosphorylates the activated forms of G protein-coupled receptors thus initiating their deactivation. It has also been shown to play a role in regulating the motility of polymorphonuclear leukocytes (PMNs).

G protein-coupled receptor kinase 5

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).

Adenylate cyclase-modulating G protein-coupled receptor signaling pathway Source: ProtInc
Apoptotic process Source: UniProtKB-KW
G protein-coupled receptor signaling pathway Source: Reactome
Negative regulation of apoptotic process Source: UniProtKB
Positive regulation of cell population proliferation Source: CACAO
Protein autophosphorylation Source: UniProtKB
Protein phosphorylation Source: GO_Central
Regulation of cell cycle Source: CACAO
Regulation of G protein-coupled receptor signaling pathway Source: ProtInc
Regulation of signal transduction Source: GO_Central
Tachykinin receptor signaling pathway Source: BHF-UCL
Wnt signaling pathway Source: UniProtKB-KW

Cell membrane; Nucleus; Cytoplasm. Predominantly localized at the plasma membrane; targeted to the cell surface through the interaction with phospholipids. Nucleus localization is regulated in a GPCR and Ca2+/calmodulin-dependent fashion.

Autophosphorylated. Autophosphorylation may play a critical role in the regulation of GRK5 kinase activity.