G protein-coupled receptor kinase 3
| GRK3 | |||
|---|---|---|---|
| Identifiers | |||
Gene ontology | |||
| Molecular function | |||
| Cellular component | |||
| Biological process | |||
| Sources:Amigo / QuickGO | |||
Ensembl | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| UniProt | |||||||||
| RefSeq (mRNA) | |||||||||
| RefSeq (protein) | |||||||||
| Location (UCSC) | Chr 22: 25.56 – 25.73 Mb | Chr 5: 113.06 – 113.16 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
| View/Edit Human | View/Edit Mouse |
G-protein-coupled receptor kinase 3 (GRK3) is an
GRK2.[6]
Function
G protein-coupled receptor kinases phosphorylate activated G protein-coupled receptors, which promotes the binding of an arrestin protein to the receptor. Arrestin binding to phosphorylated, active receptor prevents receptor stimulation of heterotrimeric G protein transducer proteins, blocking their cellular signaling and resulting in receptor desensitization. Arrestin binding also directs receptors to specific cellular internalization pathways, removing the receptors from the cell surface and also preventing additional activation. Arrestin binding to phosphorylated, active receptor also enables receptor signaling through arrestin partner proteins. As a result, the G protein-coupled receptors' complicated signaling switch is the GRK/arrestin system.[7]
GRK3 and the closely related GRK2 phosphorylate receptors at sites that encourage arrestin-mediated receptor desensitization, internalization and trafficking rather than arrestin-mediated signaling (in contrast to
biased agonism (also called functional selectivity), where a drug binding to a receptor may bias that receptor's signaling toward a particular subset of the actions stimulated by that receptor.[10][11]
GRK3 is expressed broadly in tissues, but generally at lower levels than the related GRK2.immunodeficient WHIM syndrome in humans, and appears causative in a mouse model of the disease.[18][19]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000100077 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000042249 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 7695743.
- PMID 1869533.
- PMID 30837883.
- PMID 15671181.
- PMID 15671180.
- PMID 19497875.
- PMID 30131371.
- PMID 1403099.
- PMID 8276821.
- PMID 29884935.
- S2CID 26066432.
- S2CID 43214075.
- PMID 26043205.
- PMID 18274673.
- PMID 23935208.
Further reading
- Benovic JL, Onorato JJ, Arriza JL, Stone WC, Lohse M, Jenkins NA, Gilbert DJ, Copeland NG, Caron MG, Lefkowitz RJ (August 1991). "Cloning, expression, and chromosomal localization of beta-adrenergic receptor kinase 2. A new member of the receptor kinase family". The Journal of Biological Chemistry. 266 (23): 14939–46. PMID 1869533.
- Parruti G, Ambrosini G, Sallese M, De Blasi A (January 1993). "Molecular cloning, functional expression and mRNA analysis of human beta-adrenergic receptor kinase 2". Biochemical and Biophysical Research Communications. 190 (2): 475–81. PMID 8427589.
- Oppermann M, Freedman NJ, Alexander RW, Lefkowitz RJ (May 1996). "Phosphorylation of the type 1A angiotensin II receptor by G protein-coupled receptor kinases and protein kinase C". The Journal of Biological Chemistry. 271 (22): 13266–72. PMID 8662816.
- Premont RT, Claing A, Vitale N, Freeman JL, Pitcher JA, Patton WA, Moss J, Vaughan M, Lefkowitz RJ (November 1998). "beta2-Adrenergic receptor regulation by GIT1, a G protein-coupled receptor kinase-associated ADP ribosylation factor GTPase-activating protein". Proceedings of the National Academy of Sciences of the United States of America. 95 (24): 14082–7. PMID 9826657.
- Oppermann M, Mack M, Proudfoot AE, Olbrich H (March 1999). "Differential effects of CC chemokines on CC chemokine receptor 5 (CCR5) phosphorylation and identification of phosphorylation sites on the CCR5 carboxyl terminus". The Journal of Biological Chemistry. 274 (13): 8875–85. PMID 10085131.
- Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP (December 1999). "The DNA sequence of human chromosome 22". Nature. 402 (6761): 489–95. PMID 10591208.
- Inngjerdingen M, Damaj B, Maghazachi AA (April 2000). "Human NK cells express CC chemokine receptors 4 and 8 and respond to thymus and activation-regulated chemokine, macrophage-derived chemokine, and I-309". Journal of Immunology. 164 (8): 4048–54. PMID 10754297.
- Celver JP, Lowe J, Kovoor A, Gurevich VV, Chavkin C (February 2001). "Threonine 180 is required for G-protein-coupled receptor kinase 3- and beta-arrestin 2-mediated desensitization of the mu-opioid receptor in Xenopus oocytes". The Journal of Biological Chemistry. 276 (7): 4894–900. PMID 11060299.
- Blaukat A, Pizard A, Breit A, Wernstedt C, Alhenc-Gelas F, Muller-Esterl W, Dikic I (November 2001). "Determination of bradykinin B2 receptor in vivo phosphorylation sites and their role in receptor function". The Journal of Biological Chemistry. 276 (44): 40431–40. PMID 11517230.
- Wang J, Guan E, Roderiquez G, Calvert V, Alvarez R, Norcross MA (December 2001). "Role of tyrosine phosphorylation in ligand-independent sequestration of CXCR4 in human primary monocytes-macrophages". The Journal of Biological Chemistry. 276 (52): 49236–43. PMID 11668182.
- Obara K, Arai K, Tomita Y, Hatano A, Takahashi K (October 2001). "G-protein coupled receptor kinase 2 and 3 expression in human detrusor cultured smooth muscle cells". Urological Research. 29 (5): 325–9. S2CID 20860391.
- Mandyam CD, Thakker DR, Christensen JL, Standifer KM (August 2002). "Orphanin FQ/nociceptin-mediated desensitization of opioid receptor-like 1 receptor and mu opioid receptors involves protein kinase C: a molecular mechanism for heterologous cross-talk". The Journal of Pharmacology and Experimental Therapeutics. 302 (2): 502–9. S2CID 16475164.
- Barrett TB, Hauger RL, Kennedy JL, Sadovnick AD, Remick RA, Keck PE, McElroy SL, Alexander M, Shaw SH, Kelsoe JR (May 2003). "Evidence that a single nucleotide polymorphism in the promoter of the G protein receptor kinase 3 gene is associated with bipolar disorder". Molecular Psychiatry. 8 (5): 546–57. S2CID 26066432.
- Dzimiri N, Muiya P, Andres E, Al-Halees Z (April 2004). "Differential functional expression of human myocardial G protein receptor kinases in left ventricular cardiac diseases". European Journal of Pharmacology. 489 (3): 167–77. PMID 15087239.
- Teli T, Markovic D, Levine MA, Hillhouse EW, Grammatopoulos DK (February 2005). "Regulation of corticotropin-releasing hormone receptor type 1alpha signaling: structural determinants for G protein-coupled receptor kinase-mediated phosphorylation and agonist-mediated desensitization". Molecular Endocrinology. 19 (2): 474–90. S2CID 22064538.
- Feng YH, Wang L, Wang Q, Li X, Zeng R, Gorodeski GI (June 2005). "ATP stimulates GRK-3 phosphorylation and beta-arrestin-2-dependent internalization of P2X7 receptor". American Journal of Physiology. Cell Physiology. 288 (6): C1342-56. PMID 15728711.
External links
- Online version of the paper in Molecular Psychiatry
- PubMed abstract
- Report from sciencedaily.com
- Human ADRBK2 genome location and ADRBK2 gene details page in the UCSC Genome Browser.
