G protein-coupled receptor kinase 6, also known as G protein-coupled receptor kinase GRK6, GRK6 and GPRK6, is a lipid-anchor protein which belongs to the protein kinase superfamily, AGC Ser/Thr protein kinase family and GPRK subfamily. GRK6 / GPRK6 contains one AGC-kinase C-terminal domain, one protein kinase domain and one RGS domain. This protein phosphorylates the activated forms of G protein-coupled receptors thus initiating their deactivation. Several transcript variants encoding different isoforms have been described. GRK6 / GPRK6 is widely expressed. GRK6 / GPRK6 silencing causes suppression of signal transducer and activator of transcription 3 (STAT3) phosphorylation associated with reduction in MCL1 levels and phosphorylation, illustrating a potent mechanism for the cytotoxicity of GRK6 inhibition in multiple myeloma (MM) tumor cells. GRK6 also appears to be involved in responses to morphine. Inhibition of GRK6 represents a uniquely targeted novel therapeutic strategy in human multiple myeloma.
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