GRK5 Protein, Human (Inactive, sf9, His, GST)

GRK5 is a serine/threonine kinase that preferentially phosphorylates the activated forms of various G-protein-coupled receptors (GPCRs). This receptor phosphorylation initiates β-arrestin-mediated receptor desensitization, internalization, and signaling events, leading to their down-regulation. GRK5 phosphorylates multiple GPCRs, including adrenergic receptors, muscarinic acetylcholine receptors (specifically Gi-coupled M2/M4 subtypes), dopamine receptors, and opioid receptors. Additionally, GRK5 phosphorylates other substrates such as 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)) leads to nuclear export of HDAC5, allowing MEF2-mediated transcription. Phosphorylation of TP53/p53, a crucial tumor suppressor, inhibits TP53/p53-mediated apoptosis. Phosphorylation of ST13 regulates the internalization of chemokine receptors. GRK5 also phosphorylates rhodopsin (RHO) (in vitro) and the non-G-protein-coupled receptor LRP6 during Wnt signaling (in vitro).