GRK2

Summary

Gene Symbol: GRK2
Description: G protein-coupled receptor kinase 2
Alias: ADRBK1, BARK1, BETA-ARK1, beta-adrenergic receptor kinase 1, adrenergic beta receptor kinase 1, beta-ARK-1
Species: human
Products:     GRK2

Top Publications

  1. Breton B, Lagacé M, Bouvier M. Combining resonance energy transfer methods reveals a complex between the alpha2A-adrenergic receptor, Galphai1beta1gamma2, and GRK2. FASEB J. 2010;24:4733-43 pubmed publisher
    ..analysis revealed that stimulation of the ?(2A)-adrenergic receptor (?(2A)AR) leads to the recruitment of GRK2 at a receptor still associated with the G?(i1)?(1)?(2) complex. The interaction kinetics of GRKs with G?(2) (2...
  2. Métayé T, Menet E, Guilhot J, Kraimps J. Expression and activity of g protein-coupled receptor kinases in differentiated thyroid carcinoma. J Clin Endocrinol Metab. 2002;87:3279-86 pubmed
    ..b>GRK2 and GRK5 were found as the predominant isoforms in the human thyroid...
  3. Bychkov E, Ahmed M, Gurevich V, Benovic J, Gurevich E. Reduced expression of G protein-coupled receptor kinases in schizophrenia but not in schizoaffective disorder. Neurobiol Dis. 2011;44:248-58 pubmed publisher
    ..The data suggest distinct molecular mechanisms underlying schizophrenia and schizoaffective disorder. ..
  4. Chen Y, Long H, Wu Z, Jiang X, Ma L. EGF transregulates opioid receptors through EGFR-mediated GRK2 phosphorylation and activation. Mol Biol Cell. 2008;19:2973-83 pubmed publisher
    ..that activation of epidermal growth factor receptor (EGFR), a member of receptor tyrosine kinase family, stimulates GRK2 activity and transregulates the function of G protein-coupled opioid receptors...
  5. Penela P, Rivas V, Salcedo A, Mayor F. G protein-coupled receptor kinase 2 (GRK2) modulation and cell cycle progression. Proc Natl Acad Sci U S A. 2010;107:1118-23 pubmed publisher
    ..G protein-coupled receptor kinase 2 (GRK2) plays a central role in G protein-coupled receptor regulation...
  6. Garcia Sevilla J, Alvaro Bartolomé M, Diez Alarcia R, Ramos Miguel A, Puigdemont D, Perez V, et al. Reduced platelet G protein-coupled receptor kinase 2 in major depressive disorder: antidepressant treatment-induced upregulation of GRK2 protein discriminates between responder and non-responder patients. Eur Neuropsychopharmacol. 2010;20:721-30 pubmed publisher
    ..Previous studies have reported that the basal status of GRK2 is different in brains (upregulation) and platelets (downregulation) of subjects with MDD...
  7. Oppermann M, Mack M, Proudfoot A, Olbrich H. Differential effects of CC chemokines on CC chemokine receptor 5 (CCR5) phosphorylation and identification of phosphorylation sites on the CCR5 carboxyl terminus. J Biol Chem. 1999;274:8875-85 pubmed
    ..In permeabilized rat basophilic leukemia CCR5 cells, monoclonal antibodies with specificity for GRK2/3 inhibited RANTES-induced receptor phosphorylation...
  8. Kavelaars A, Eijkelkamp N, Willemen H, Wang H, Carbajal A, Heijnen C. Microglial GRK2: a novel regulator of transition from acute to chronic pain. Brain Behav Immun. 2011;25:1055-60 pubmed publisher
    ..In this review, we will summarize recent evidence that a kinase known as G protein-coupled receptor kinase (GRK2) is a key regulator of the transition from acute to chronic inflammatory pain...
  9. Pitcher J, Tesmer J, Freeman J, Capel W, Stone W, Lefkowitz R. Feedback inhibition of G protein-coupled receptor kinase 2 (GRK2) activity by extracellular signal-regulated kinases. J Biol Chem. 1999;274:34531-4 pubmed
    ..Here we identify a novel mechanism whereby the activity of GRK2 is regulated by feedback inhibition. GRK2 is demonstrated to be a phosphoprotein in cells...

More Information

Publications97

  1. Freedman N, Kim L, Murray J, Exum S, Brian L, Wu J, et al. Phosphorylation of the platelet-derived growth factor receptor-beta and epidermal growth factor receptor by G protein-coupled receptor kinase-2. Mechanisms for selectivity of desensitization. J Biol Chem. 2002;277:48261-9 pubmed
    ..One such kinase, G protein-coupled receptor kinase-2 (GRK2), is known to mediate agonist-dependent phosphorylation and desensitization of multiple heptahelical receptors...
  2. Salcedo A, Mayor F, Penela P. Mdm2 is involved in the ubiquitination and degradation of G-protein-coupled receptor kinase 2. EMBO J. 2006;25:4752-62 pubmed
    G-protein-coupled receptor kinase 2 (GRK2) is a central regulator of G-protein-coupled receptor signaling...
  3. Cant S, Pitcher J. G protein-coupled receptor kinase 2-mediated phosphorylation of ezrin is required for G protein-coupled receptor-dependent reorganization of the actin cytoskeleton. Mol Biol Cell. 2005;16:3088-99 pubmed
    G protein-coupled receptor kinase 2 (GRK2) phosphorylates and desensitizes activated G protein-coupled receptors (GPCRs). Here, we identify ezrin as a novel non-GPCR substrate of GRK2...
  4. Day P, Carman C, Sterne Marr R, Benovic J, Wedegaertner P. Differential interaction of GRK2 with members of the G alpha q family. Biochemistry. 2003;42:9176-84 pubmed
    ..Recently, it was shown that the G protein-coupled receptor kinase 2 (GRK2) contains an RGS domain that binds to the active form of G alpha(q)...
  5. Fusco A, Santulli G, Sorriento D, Cipolletta E, Garbi C, Dorn G, et al. Mitochondrial localization unveils a novel role for GRK2 in organelle biogenesis. Cell Signal. 2012;24:468-75 pubmed publisher
    ..such as insulin and insulin like growth factor cause cellular accumulation of G protein coupled receptor kinase 2 (GRK2), which in turn is able to induce insulin resistance...
  6. Prossnitz E, Kim C, Benovic J, Ye R. Phosphorylation of the N-formyl peptide receptor carboxyl terminus by the G protein-coupled receptor kinase, GRK2. J Biol Chem. 1995;270:1130-7 pubmed
    ..phosphorylated by a neutrophil cytosolic kinase with properties similar to the G protein-coupled receptor kinase, GRK2. Both kinase activities show a lack of sensitivity toward protein kinase A, protein kinase C, and tyrosine kinase ..
  7. Pronin A, Morris A, Surguchov A, Benovic J. Synucleins are a novel class of substrates for G protein-coupled receptor kinases. J Biol Chem. 2000;275:26515-22 pubmed
    ..We found that all synucleins are GRK substrates, with GRK2 preferentially phosphorylating the alpha and beta isoforms, whereas GRK5 prefers alpha-synuclein as a substrate...
  8. Jorgensen R, Holliday N, Hansen J, Vrecl M, Heding A, Schwartz T, et al. Characterization of G-protein coupled receptor kinase interaction with the neurokinin-1 receptor using bioluminescence resonance energy transfer. Mol Pharmacol. 2008;73:349-58 pubmed
    ..bioluminescence resonance energy transfer(2) (BRET(2)) measurements between the family A NK-1 receptor and GRK2 and GRK5 as well as their respective kinase-inactive mutants...
  9. Ruiz Gomez A, Humrich J, Murga C, Quitterer U, Lohse M, Mayor F. Phosphorylation of phosducin and phosducin-like protein by G protein-coupled receptor kinase 2. J Biol Chem. 2000;275:29724-30 pubmed
    G protein-coupled receptor kinase 2 (GRK2) is able to phosphorylate a variety of agonist-occupied G protein-coupled receptors (GPCR) and plays an important role in GPCR modulation...
  10. Sterne Marr R, Leahey P, Bresee J, Dickson H, Ho W, Ragusa M, et al. GRK2 activation by receptors: role of the kinase large lobe and carboxyl-terminal tail. Biochemistry. 2009;48:4285-93 pubmed publisher
    ..To initiate a study of GRK2 activation, we sought to identify sites on GRK2 remote from the active site that are involved in interactions with ..
  11. Cipolletta E, Campanile A, Santulli G, Sanzari E, Leosco D, Campiglia P, et al. The G protein coupled receptor kinase 2 plays an essential role in beta-adrenergic receptor-induced insulin resistance. Cardiovasc Res. 2009;84:407-15 pubmed publisher
    ..The cellular levels of G protein coupled receptor kinase 2 (GRK2) increase during chronic betaAR stimulation, leading to betaAR desensitization...
  12. Carman C, Barak L, Chen C, Liu Chen L, Onorato J, Kennedy S, et al. Mutational analysis of Gbetagamma and phospholipid interaction with G protein-coupled receptor kinase 2. J Biol Chem. 2000;275:10443-52 pubmed
    ..b>GRK2 and GRK3 are selectively regulated in vitro by free Gbetagamma subunits and negatively charged membrane ..
  13. Violin J, DeWire S, Barnes W, Lefkowitz R. G protein-coupled receptor kinase and beta-arrestin-mediated desensitization of the angiotensin II type 1A receptor elucidated by diacylglycerol dynamics. J Biol Chem. 2006;281:36411-9 pubmed
  14. Eijkelkamp N, Wang H, Garza Carbajal A, Willemen H, Zwartkruis F, Wood J, et al. Low nociceptor GRK2 prolongs prostaglandin E2 hyperalgesia via biased cAMP signaling to Epac/Rap1, protein kinase Cepsilon, and MEK/ERK. J Neurosci. 2010;30:12806-15 pubmed publisher
    ..Here we describe a completely novel mechanism via which nociceptor G-protein-coupled receptor kinase 2 (GRK2) contributes to regulation of inflammatory hyperalgesia...
  15. Peregrin S, Jurado Pueyo M, Campos P, Sanz Moreno V, Ruiz Gomez A, Crespo P, et al. Phosphorylation of p38 by GRK2 at the docking groove unveils a novel mechanism for inactivating p38MAPK. Curr Biol. 2006;16:2042-7 pubmed
    ..We report that GRK2 is a novel inactivating kinase of p38MAPK...
  16. Iwata K, Luo J, Penn R, Benovic J. Bimodal regulation of the human H1 histamine receptor by G protein-coupled receptor kinase 2. J Biol Chem. 2005;280:2197-204 pubmed
    ..Overexpression of GRK2 promoted H1HR phosphorylation in intact HEK293 cells and completely inhibited inositol phosphate production ..
  17. Freeman J, Gonzalo P, Pitcher J, Claing A, Lavergne J, Reboud J, et al. Beta 2-adrenergic receptor stimulated, G protein-coupled receptor kinase 2 mediated, phosphorylation of ribosomal protein P2. Biochemistry. 2002;41:12850-7 pubmed
    ..phosphorylating the beta2-adrenergic receptor (beta2AR) and other receptors, G protein-coupled receptor kinase 2 (GRK2) can also phosphorylate tubulin, a nonreceptor substrate...
  18. Cong M, Perry S, Lin F, Fraser I, Hu L, Chen W, et al. Regulation of membrane targeting of the G protein-coupled receptor kinase 2 by protein kinase A and its anchoring protein AKAP79. J Biol Chem. 2001;276:15192-9 pubmed
    ..Here we show that AKAP79 also regulates the ability of GRK2 to phosphorylate agonist-occupied receptors...
  19. Polhemus D, Gao J, Scarborough A, Trivedi R, McDonough K, Goodchild T, et al. Radiofrequency Renal Denervation Protects the Ischemic Heart via Inhibition of GRK2 and Increased Nitric Oxide Signaling. Circ Res. 2016;119:470-80 pubmed publisher
    ..These findings provide new insights into the remote cardioprotective effects of RF-RDN acting directly on cardiac myocytes to attenuate cell death and protect against ischemic injury. ..
  20. Tsai W, Lu Y, Chen Y, Chang C, Kao Y, Lin Y, et al. Ablation of androgen receptor gene triggers right ventricular outflow tract ventricular tachycardia. Int J Cardiol. 2015;189:172-81 pubmed publisher
    ..2, NCX, phosphorylated RyR (s2814), phosphorylated phospholamban (Thr17), CAMKII and GRK2 than WT RVOT myocytes...
  21. Zhu F, Ji X, Zhong X, Hu H, Liang L, Chen J, et al. [Effects of mild hypothermia on β-adrenergic signaling pathway in a cardiac arrest swine model]. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2018;30:134-139 pubmed publisher
    ..detected by enzyme linked immunosorbent assay (ELISA), the protein content of G protein-coupled receptor kinase 2 (GRK2) was detected by Western Blot...
  22. Morshed S, Ma R, Latif R, Davies T. Biased signaling by thyroid-stimulating hormone receptor-specific antibodies determines thyrocyte survival in autoimmunity. Sci Signal. 2018;11: pubmed publisher
    ..to normal vesicular trafficking of TSHR through the activation of major G proteins, the C-TSHR-Abs resulted in GRK2- and β-arrestin-1-dependent biased signaling, which is interpreted as a danger signal by the cell...
  23. Mushegian A, Gurevich V, Gurevich E. The origin and evolution of G protein-coupled receptor kinases. PLoS ONE. 2012;7:e33806 pubmed publisher
    ..GRKs in Metazoa fall into two clades, one including GRK2 and GRK3, and the other consisting of all remaining GRKs, split into GRK1-GRK7 lineage and GRK4-GRK5-GRK6 lineage ..
  24. Pusapati G, Kong J, Patel B, Gouti M, Sagner A, Sircar R, et al. G protein-coupled receptors control the sensitivity of cells to the morphogen Sonic Hedgehog. Sci Signal. 2018;11: pubmed publisher
    ..in SMO signaling: the heterotrimeric G protein subunit GαS, the G protein-coupled receptor kinase 2 (GRK2), and the GαS-coupled receptor GPR161...
  25. Rengo G, Pagano G, Filardi P, Femminella G, Parisi V, Cannavo A, et al. Prognostic Value of Lymphocyte G Protein-Coupled Receptor Kinase-2 Protein Levels in Patients With Heart Failure. Circ Res. 2016;118:1116-24 pubmed publisher
    ..Myocardial G protein-coupled receptor kinase-2 (GRK2) is upregulated in HF patients, causing dysfunctional β-adrenergic receptor signaling...
  26. Mehta N, Cheng A, Chiang C, Mendoza Viveros L, Ling H, Patel A, et al. GRK2 Fine-Tunes Circadian Clock Speed and Entrainment via Transcriptional and Post-translational Control of PERIOD Proteins. Cell Rep. 2015;12:1272-88 pubmed publisher
    ..Here, we reveal that G-protein-coupled receptor kinase 2 (GRK2) modulates the period, amplitude, and entrainment characteristics of the SCN...
  27. Gatto F, Feelders R, van der Pas R, Kros J, Dogan F, van Koetsveld P, et al. ?-Arrestin 1 and 2 and G protein-coupled receptor kinase 2 expression in pituitary adenomas: role in the regulation of response to somatostatin analogue treatment in patients with acromegaly. Endocrinology. 2013;154:4715-25 pubmed publisher
    ..Our aim was to characterize GRK2 and ?-arrestins expression in different pituitary adenomas and to investigate their potential role in the response ..
  28. Freeman K, Colon Rivera C, Olsson M, Moore R, Weinberger H, Grupp I, et al. Progression from hypertrophic to dilated cardiomyopathy in mice that express a mutant myosin transgene. Am J Physiol Heart Circ Physiol. 2001;280:H151-9 pubmed
    ..We conclude that transgenic male animals have undergone cardiac decompensation resulting in a DCM phenotype. This supports the idea that HCM and DCM may be part of a pathological continuum rather than independent diseases...
  29. Yu P, Yang Z, Jones J, Wang Z, Owens S, Mueller S, et al. D1 dopamine receptor signaling involves caveolin-2 in HEK-293 cells. Kidney Int. 2004;66:2167-80 pubmed
    ..The majority of hD1Rs are distributed in lipid rafts. Heterologously and endogenously expressed D1Rs in renal cells are associated with and regulated by caveolin-2. ..
  30. Theccanat T, Philip J, Razzaque A, Ludmer N, Li J, Xu X, et al. Regulation of cellular oxidative stress and apoptosis by G protein-coupled receptor kinase-2; The role of NADPH oxidase 4. Cell Signal. 2016;28:190-203 pubmed publisher
    ..We hypothesize that GRK2, a critical regulator of myocardial β-AR signaling, plays an important role in mediating cellular oxidative ..
  31. Ho J, Cocolakis E, Dumas V, Posner B, Laporte S, Lebrun J. The G protein-coupled receptor kinase-2 is a TGFbeta-inducible antagonist of TGFbeta signal transduction. EMBO J. 2005;24:3247-58 pubmed
    ..In this study, we identify the protein G-coupled receptor kinase 2 (GRK2), a kinase involved in the desensitization of G protein-coupled receptors (GPCR), as a downstream target and ..
  32. Rockman H, Chien K, Choi D, Iaccarino G, Hunter J, Ross J, et al. Expression of a beta-adrenergic receptor kinase 1 inhibitor prevents the development of myocardial failure in gene-targeted mice. Proc Natl Acad Sci U S A. 1998;95:7000-5 pubmed
    ..These findings implicate abnormal betaAR-G protein coupling in the pathogenesis of the failing heart and point the way toward development of agents to inhibit betaARK1 as a novel mode of therapy. ..
  33. Zhang F, Xiang S, Cao Y, Li M, Ma Q, Liang H, et al. EIF3D promotes gallbladder cancer development by stabilizing GRK2 kinase and activating PI3K-AKT signaling pathway. Cell Death Dis. 2017;8:e2868 pubmed publisher
    ..In details, eIF3d stabilizes GRK2 protein by blocking ubiquitin-mediated degradation, consequently activates PI3K/Akt signaling, and promotes GBC ..
  34. Liu S, Premont R, Singh S, Rockey D. Caveolin 1 and G-Protein-Coupled Receptor Kinase-2 Coregulate Endothelial Nitric Oxide Synthase Activity in Sinusoidal Endothelial Cells. Am J Pathol. 2017;187:896-907 pubmed publisher
    ..eNOS activity in sinusoidal endothelial cells (SECs) via its interaction with G-protein-coupled receptor kinase-2 (GRK2) that also post-translationally modifies eNOS...
  35. Fu Q, Wang Q, Xiang Y. Insulin and ? Adrenergic Receptor Signaling: Crosstalk in Heart. Trends Endocrinol Metab. 2017;28:416-427 pubmed publisher
    ..insulin stimulation crosstalks with cardiac ?AR via InsR substrate (IRS)-dependent and G-protein receptor kinase 2 (GRK2)-mediated phosphorylation of ?2AR...
  36. Vinge L, Øie E, Andersson Y, Grøgaard H, Andersen G, Attramadal H. Myocardial distribution and regulation of GRK and beta-arrestin isoforms in congestive heart failure in rats. Am J Physiol Heart Circ Physiol. 2001;281:H2490-9 pubmed
    Myocardial G protein-coupled receptor kinase 2 (GRK2) has been shown to be involved in the pathophysiology of congestive heart failure (CHF)...
  37. Inngjerdingen M, Damaj B, Maghazachi A. Human NK cells express CC chemokine receptors 4 and 8 and respond to thymus and activation-regulated chemokine, macrophage-derived chemokine, and I-309. J Immunol. 2000;164:4048-54 pubmed
    ..These results suggest that TARC utilizes CCR4 and CCR8. Our results are the first to show that IL-2-activated NK cells express CCR4 and CCR8, suggesting that these receptors are not exclusive for Th2 cells. ..
  38. Hullmann J, Traynham C, Coleman R, Koch W. The expanding GRK interactome: Implications in cardiovascular disease and potential for therapeutic development. Pharmacol Res. 2016;110:52-64 pubmed publisher
    ..GRKs 2 and 5 are highly expressed in the heart, and known to be upregulated in HF. Over the last 20 years, both GRK2 and GRK5 have been demonstrated to be critical mediators of the molecular alterations that occur in the failing ..
  39. Mayor F, Cruces Sande M, Arcones A, Vila Bedmar R, Briones A, Salaices M, et al. G protein-coupled receptor kinase 2 (GRK2) as an integrative signalling node in the regulation of cardiovascular function and metabolic homeostasis. Cell Signal. 2018;41:25-32 pubmed publisher
    G protein-coupled receptor kinase 2 (GRK2) is emerging as a pivotal signalling hub able to integrate different transduction cascades. This ability appears to underlie its central role in different physiological and pathological conditions...
  40. Le Sommer C, Barrows N, Bradrick S, Pearson J, Garcia Blanco M. G protein-coupled receptor kinase 2 promotes flaviviridae entry and replication. PLoS Negl Trop Dis. 2012;6:e1820 pubmed publisher
    ..The YFV host candidate GRK2 (also known as ADRBK1) was validated both in siRNA-mediated knockdown HuH-7 cells and in GRK(-/-) mouse embryonic fibroblasts...
  41. Leosco D, Fortunato F, Rengo G, Iaccarino G, Sanzari E, Golino L, et al. Lymphocyte G-protein-coupled receptor kinase-2 is upregulated in patients with Alzheimer's disease. Neurosci Lett. 2007;415:279-82 pubmed
    ..The G-protein-coupled receptor kinase-2 (GRK2) plays an important role in regulating the GPCRs signaling: its increased expression is associated with receptor ..
  42. Hennenberg M, Trebicka J, Biecker E, Schepke M, Sauerbruch T, Heller J. Vascular dysfunction in human and rat cirrhosis: role of receptor-desensitizing and calcium-sensitizing proteins. Hepatology. 2007;45:495-506 pubmed
    ..Our data suggest that in cirrhosis-induced vasodilation, the AT1-R is desensitized by GRK-2 and beta-arrestin-2 and that changed patterns of phosphorylated Ca(2+) sensitizing proteins decrease Ca(2+) sensitivity. ..
  43. Daniele S, Trincavelli M, Fumagalli M, Zappelli E, Lecca D, Bonfanti E, et al. Does GRK-? arrestin machinery work as a "switch on" for GPR17-mediated activation of intracellular signaling pathways?. Cell Signal. 2014;26:1310-25 pubmed publisher
    ..CysLT-mediated receptor desensitization mainly involved GRK2; this kinase, via a G protein-dependent mechanism, promoted a transient binding of the receptor to ?-arrestins, ..
  44. Lymperopoulos A, Brill A, McCrink K. GPCRs of adrenal chromaffin cells & catecholamines: The plot thickens. Int J Biochem Cell Biol. 2016;77:213-9 pubmed publisher
    ..Most prominent among these are GRK2 and β-arrestin1, which are known to interact with GPCRs regulating receptor signaling and function...
  45. Beautrait A, Michalski K, Lopez T, Mannix K, McDonald D, Cutter A, et al. Mapping the putative G protein-coupled receptor (GPCR) docking site on GPCR kinase 2: insights from intact cell phosphorylation and recruitment assays. J Biol Chem. 2014;289:25262-75 pubmed publisher
    ..We also developed a bioluminescence resonance energy transfer-based assay to monitor the recruitment of GRK2 to activated ?(2A)-adrenergic receptors (?(2A)ARs) in living cells...
  46. Williams M, Hata J, Schroder J, Rampersaud E, Petrofski J, Jakoi A, et al. Targeted beta-adrenergic receptor kinase (betaARK1) inhibition by gene transfer in failing human hearts. Circulation. 2004;109:1590-3 pubmed
    ..Thus, betaARK1 inhibition may represent a therapeutic strategy for human HF. ..
  47. Bernardo B, Blaxall B. From Bench to Bedside: New Approaches to Therapeutic Discovery for Heart Failure. Heart Lung Circ. 2016;25:425-34 pubmed publisher
    ..RNAs, angiotensin receptor-neprilysin inhibitors, cardiac myosin activators, BGP-15 and molecules targeting GRK2 including M119, gallein and paroxetine...
  48. Ni W, Tang L, Zhou H, Ding H, Qiu Y. Renoprotective effect of berberine via regulating the PGE2 -EP1-G?q-Ca(2+) signalling pathway in glomerular mesangial cells of diabetic rats. J Cell Mol Med. 2016;20:1491-502 pubmed publisher
    ..The expression of the EP1 receptor and the roles of GRK2 and ?-arrestin2 were identified using western blotting and flow cytometry...
  49. dela Paz N, Melchior B, Frangos J. Shear stress induces Gαq/11 activation independently of G protein-coupled receptor activation in endothelial cells. Am J Physiol Cell Physiol. 2017;312:C428-C437 pubmed publisher
    ..from its receptor S1P3, followed by an increased association within 2 min of GPCR kinase-2 (GRK2) and β-arrestin-1/2 with S1P3 in human coronary artery ECs, which are consistent with GPCR/Gα..
  50. Menard L, Ferguson S, Barak L, Bertrand L, Premont R, Colapietro A, et al. Members of the G protein-coupled receptor kinase family that phosphorylate the beta2-adrenergic receptor facilitate sequestration. Biochemistry. 1996;35:4155-60 pubmed
    ..phosphorylation; however, its ability to be phosphorylated and sequestered could be restored by overexpressing GRK2 [Ferguson et al. (1995) J. Biol. Chem. 270, 24782]...
  51. Allen S, Parthasarathy G, Darke P, Diehl R, Ford R, Hall D, et al. Structure and Function of the Hypertension Variant A486V of G Protein-coupled Receptor Kinase 4. J Biol Chem. 2015;290:20360-73 pubmed publisher
    ..In this respect, GRK4α is more similar to GRK2 than GRK6...
  52. Suo W, Li L. Dysfunction of G protein-coupled receptor kinases in Alzheimer's disease. ScientificWorldJournal. 2010;10:1667-78 pubmed publisher
    ..Recent studies have indicated the possible involvement of GRK, primarily GRK2 and GRK5, dysfunction in the pathogenesis of AD...
  53. Barthet G, Gaven F, Framery B, Shinjo K, Nakamura T, Claeysen S, et al. Uncoupling and endocytosis of 5-hydroxytryptamine 4 receptors. Distinct molecular events with different GRK2 requirements. J Biol Chem. 2005;280:27924-34 pubmed
    ..significant uncoupling was observed in COS-7 or HEK293 cells, which expressed either no or a weak concentration of GRK2, respectively...
  54. Gärtner F, Seidel T, Schulz U, Gummert J, Milting H. Desensitization and internalization of endothelin receptor A: impact of G protein-coupled receptor kinase 2 (GRK2)-mediated phosphorylation. J Biol Chem. 2013;288:32138-48 pubmed publisher
    Endothelin receptor A (ETA), a G protein-coupled receptor, mediates endothelin signaling, which is regulated by GRK2. Three Ser and seven Thr residues recently proven to be phosphoacceptor sites are located in the C-terminal extremity (..
  55. Fumagalli M, Bonfanti E, Daniele S, Zappelli E, Lecca D, Martini C, et al. The ubiquitin ligase Mdm2 controls oligodendrocyte maturation by intertwining mTOR with G protein-coupled receptor kinase 2 in the regulation of GPR17 receptor desensitization. Glia. 2015;63:2327-39 pubmed publisher
    ..In maturing OPCs, both rapamycin and Nutlin-3, a small molecule inhibitor of Mdm2-p53 interactions, increased GRK2 sequestration by Mdm2, leading to impaired GPR17 down-regulation and OPC maturation block...
  56. Kenski D, Zhang C, von Zastrow M, Shokat K. Chemical genetic engineering of G protein-coupled receptor kinase 2. J Biol Chem. 2005;280:35051-61 pubmed
    ..In the present study we have developed an engineered version of GRK2 that is specifically and reversibly inhibited by the substituted nucleotide analog 1-naphthyl-PP1 (1Na-PP1), and we ..
  57. Hu M, Wang C, Li W, Lu W, Bai Z, Qin D, et al. A KSHV microRNA Directly Targets G Protein-Coupled Receptor Kinase 2 to Promote the Migration and Invasion of Endothelial Cells by Inducing CXCR2 and Activating AKT Signaling. PLoS Pathog. 2015;11:e1005171 pubmed publisher
    ..showed that miR-K3 directly targeted G protein-coupled receptor (GPCR) kinase 2 (GRK2, official gene symbol ADRBK1). Importantly, overexpression of GRK2 reversed miR-K3 induction of cell migration and invasion...
  58. Brenninkmeijer C, Price S, Lopez Bernal A, Phaneuf S. Expression of G-protein-coupled receptor kinases in pregnant term and non-pregnant human myometrium. J Endocrinol. 1999;162:401-8 pubmed
    ..Our data indicate that GRK2 is only expressed in pregnant term myometrium and is not found in non-pregnant tissue...
  59. Subramanian H, Gupta K, Parameswaran N, Ali H. Regulation of Fc?RI signaling in mast cells by G protein-coupled receptor kinase 2 and its RH domain. J Biol Chem. 2014;289:20917-27 pubmed
    ..Here, we sought to determine the role of GRK2 on Fc?RI signaling and mediator release in mast cells...
  60. Mouledous L, Froment C, Dauvillier S, Burlet Schiltz O, Zajac J, Mollereau C. GRK2 protein-mediated transphosphorylation contributes to loss of function of ?-opioid receptors induced by neuropeptide FF (NPFF2) receptors. J Biol Chem. 2012;287:12736-49 pubmed publisher
    ..Ser-377 cross-phosphorylation and MOP receptor loss of function were mediated by the G protein receptor kinase GRK2. In addition, mass spectrometric analysis revealed that the phosphorylation pattern of MOP receptors was ..
  61. Ji S, Liu X, Li S, Shen L, Li F, Wang J, et al. PH domain of G protein-coupled receptor kinase-2 binds to protein kinase C (PKC) and negatively regulates activity of PKC kinase. Front Biosci. 2003;8:a34-9 pubmed
    ..However, detail mechanism of interaction between PKC and GRK2 and the effect of GRK2 on activity of PKC remain unknown...
  62. Carman C, Lisanti M, Benovic J. Regulation of G protein-coupled receptor kinases by caveolin. J Biol Chem. 1999;274:8858-64 pubmed
    ..Based on the identification of a consensus caveolin binding motif within the pleckstrin homology domain of GRK2, we tested the direct binding of purified full-length GRK2 to various glutathione S-transferase-caveolin-1 fusion ..
  63. Sorriento D, Santulli G, Franco A, Cipolletta E, Napolitano L, Gambardella J, et al. Integrating GRK2 and NFkappaB in the Pathophysiology of Cardiac Hypertrophy. J Cardiovasc Transl Res. 2015;8:493-502 pubmed publisher
    G protein coupled receptor kinase type 2 (GRK2) plays an important role in the development and maintenance of cardiac hypertrophy and heart failure even if its exact role is still unknown...
  64. Hughes R, Anderson K, Kiel D, Insel P. Cloning of GRK2 cDNA from S49 murine lymphoma cells. Am J Physiol. 1996;270:C885-91 pubmed
    ..We have cloned GRK2 from S49 mouse lymphoma cells...
  65. Liu X, Ma B, Malik A, Tang H, Yang T, Sun B, et al. Bidirectional regulation of neutrophil migration by mitogen-activated protein kinases. Nat Immunol. 2012;13:457-64 pubmed publisher
    ..The extracellular signal-regulated kinase Erk potentiated activity of the G protein-coupled receptor kinase GRK2 and inhibited neutrophil migration, whereas the MAPK p38 acted as a noncanonical GRK that phosphorylated the formyl ..
  66. Taguchi K. [The Role of GRK2 and Its Potential as a New Therapeutic Target in Diabetic Vascular Complications]. Yakugaku Zasshi. 2015;135:961-7 pubmed publisher
    ..We identified G-protein-coupled receptor kinase 2 (GRK2) as a critical factor in diabetic endothelial dysfunction...
  67. Pao C, Benovic J. Structure/function analysis of alpha2A-adrenergic receptor interaction with G protein-coupled receptor kinase 2. J Biol Chem. 2005;280:11052-8 pubmed
    ..Here, we used the alpha2A-adrenergic receptor (alpha(2A)AR) as a model to study GRK/receptor interaction because GRK2 phosphorylation of four adjacent serines within the large third intracellular loop of this receptor is known to ..
  68. Tiruppathi C, Yan W, Sandoval R, Naqvi T, Pronin A, Benovic J, et al. G protein-coupled receptor kinase-5 regulates thrombin-activated signaling in endothelial cells. Proc Natl Acad Sci U S A. 2000;97:7440-5 pubmed
    ..b>GRK2, GRK5, and GRK6 isoforms were expressed predominantly in endothelial cells...
  69. Freedman N, Ament A, Oppermann M, Stoffel R, Exum S, Lefkowitz R. Phosphorylation and desensitization of human endothelin A and B receptors. Evidence for G protein-coupled receptor kinase specificity. J Biol Chem. 1997;272:17734-43 pubmed
    ..03) by GRK inhibition, effected by a dominant negative GRK2 mutant. Inhibition of agonist-induced phosphorylation abrogated agonist-induced ETA-R desensitization...
  70. Yang X, Zhang Y, Lai Z, Xing F, Liu Y. Pleckstrin homology domain of G protein-coupled receptor kinase-2 binds to PKC and affects the activity of PKC kinase. World J Gastroenterol. 2003;9:800-3 pubmed
    ..In the present study, GRK(2) PH domain was associated with PKC and down-regulated PKC activity, but Btk PH domain up-regulated PKC activity as compared with GRK(2) PH domain. GRK(2) can bind with PKC and down-regulated PKC activity. ..
  71. Yang J, Shen Z, Jiang X, Yang H, Huang H, Jin L, et al. Agonist-Activated Bombyx Corazonin Receptor Is Internalized via an Arrestin-Dependent and Clathrin-Independent Pathway. Biochemistry. 2016;55:3874-87 pubmed publisher
    ..Assays using RNA interference revealed that both GRK2 and GRK5 were essentially involved in the regulation of BmCrzR phosphorylation and internalization...
  72. Guccione M, Ettari R, Taliani S, Da Settimo F, Zappala M, Grasso S. G-Protein-Coupled Receptor Kinase 2 (GRK2) Inhibitors: Current Trends and Future Perspectives. J Med Chem. 2016;59:9277-9294 pubmed
    G-protein-coupled receptor kinase 2 (GRK2) is a G-protein-coupled receptor kinase that is ubiquitously expressed in many tissues and regulates various intracellular mechanisms...
  73. Huang C, Slusher A, Whitehurst M, Wells M, Mock J, Maharaj A, et al. Acute aerobic exercise mediates G protein-coupled receptor kinase 2 expression in human PBMCs. Life Sci. 2015;135:87-91 pubmed publisher
    G protein-coupled receptor kinase 2 (GRK2), a cytosolic enzyme desensitizing G protein-couple receptors (e.g...
  74. Cohn H, Xi Y, Pesant S, Harris D, Hyslop T, Falkner B, et al. G protein-coupled receptor kinase 2 expression and activity are associated with blood pressure in black Americans. Hypertension. 2009;54:71-6 pubmed publisher
    ..The 2 most abundantly expressed GRKs in the cardiovascular system are GRK2 and GRK5, and each has unique substrates...
  75. Izzo R, Cipolletta E, Ciccarelli M, Campanile A, Santulli G, Palumbo G, et al. Enhanced GRK2 expression and desensitization of betaAR vasodilatation in hypertensive patients. Clin Transl Sci. 2008;1:215-20 pubmed publisher
    Increased levels of G protein coupled receptor kinase GRK2 appear to participate in hypertension presumably through the desensitization of beta adrenergic receptors (betaARs) that mediate vasodilatation...
  76. Blake Crabb E, Franco R, Bowen M, Huang C, Caslin H, Acevedo E. G protein-coupled receptor kinase-2 in peripheral blood mononuclear cells following acute mental stress. Life Sci. 2016;145:184-9 pubmed publisher
    This study investigated G-protein-coupled receptor kinase-2 (GRK2) density in peripheral blood mononuclear cells (PBMC) and its relationship to plasma pro-inflammatory cytokine concentrations following acute mental stress...
  77. Fernandez N, Gottardo F, Alonso M, Monczor F, Shayo C, Davio C. Roles of phosphorylation-dependent and -independent mechanisms in the regulation of histamine H2 receptor by G protein-coupled receptor kinase 2. J Biol Chem. 2011;286:28697-706 pubmed publisher
    It is widely assumed that G protein-coupled receptor kinase 2 (GRK2)-mediated specific inhibition of G protein-coupled receptors (GPCRs) response involves GRK-mediated receptor phosphorylation followed by ?-arrestin binding and subsequent ..
  78. Namkung Y, Dipace C, Urizar E, Javitch J, Sibley D. G protein-coupled receptor kinase-2 constitutively regulates D2 dopamine receptor expression and signaling independently of receptor phosphorylation. J Biol Chem. 2009;284:34103-15 pubmed publisher
    We investigated the regulatory effects of GRK2 on D(2) dopamine receptor signaling and found that this kinase inhibits both receptor expression and functional signaling in a phosphorylation-independent manner, apparently through different ..
  79. Zha Z, Han X, Smith M, Liu Y, Giguère P, Kopanja D, et al. A Non-Canonical Function of Gβ as a Subunit of E3 Ligase in Targeting GRK2 Ubiquitylation. Mol Cell. 2015;58:794-803 pubmed publisher
    ..Here, we report that G protein β subunits (Gβ) bind to DDB1 and that Gβ2 targets GRK2 for ubiquitylation by the DDB1-CUL4A-ROC1 ubiquitin ligase...
  80. Chen W, Ren X, Nelson C, Barak L, Chen J, Beachy P, et al. Activity-dependent internalization of smoothened mediated by beta-arrestin 2 and GRK2. Science. 2004;306:2257-60 pubmed
    ..two molecules interact with mammalian Smo in an activation-dependent manner: G protein-coupled receptor kinase 2 (GRK2) leads to phosphorylation of Smo, and beta-arrestin 2 fused to green fluorescent protein interacts with Smo...
  81. Iacovelli L, Capobianco L, Iula M, Di Giorgi Gerevini V, Picascia A, Blahos J, et al. Regulation of mGlu4 metabotropic glutamate receptor signaling by type-2 G-protein coupled receptor kinase (GRK2). Mol Pharmacol. 2004;65:1103-10 pubmed
    We examined the role of G-protein coupled receptor kinase-2 (GRK2) in the homologous desensitization of mGlu4 metabotropic glutamate receptors transiently expressed in human embryonic kidney (HEK) 293 cells...
  82. Zhou L, Wang M, Liang Z, Zhou W, You L, Pan B, et al. G-protein-coupled receptor kinase 2 in pancreatic cancer: clinicopathologic and prognostic significance. Hum Pathol. 2016;56:171-7 pubmed publisher
    G-protein-coupled receptor kinase 2 (GRK2) was found to regulate biological behaviors in some cancers, including pancreatic cancer (PC). However, its clinicopathologic and prognostic implications in cancer remain unclear...
  83. Li J, Xiang B, Su W, Zhang X, Huang Y, Ma L. Agonist-induced formation of opioid receptor-G protein-coupled receptor kinase (GRK)-G beta gamma complex on membrane is required for GRK2 function in vivo. J Biol Chem. 2003;278:30219-26 pubmed
    ..that the binding of GRK to membrane-associated G beta gamma subunits plays an important role in translocation of GRK2 from the cytoplasm to the plasma membrane...
  84. Wei Z, Hurtt R, Gu T, Bodzin A, Koch W, Doria C. GRK2 negatively regulates IGF-1R signaling pathway and cyclins' expression in HepG2 cells. J Cell Physiol. 2013;228:1897-901 pubmed publisher
    G protein coupled receptor kinase 2 (GRK2) plays a central role in the regulation of a variety of important signaling pathways...
  85. Blaukat A, Pizard A, Breit A, Wernstedt C, Alhenc Gelas F, Muller Esterl W, et al. Determination of bradykinin B2 receptor in vivo phosphorylation sites and their role in receptor function. J Biol Chem. 2001;276:40431-40 pubmed
    ..The differential usage of clustered phosphoacceptor sites points to distinct roles of multiple kinases in controlling G protein-coupled receptor function. ..
  86. Perrino C, Schroder J, Lima B, Villamizar N, Nienaber J, Milano C, et al. Dynamic regulation of phosphoinositide 3-kinase-gamma activity and beta-adrenergic receptor trafficking in end-stage human heart failure. Circulation. 2007;116:2571-9 pubmed
    ..Importantly, mechanical unloading leads to complete reversal in PI3Kgamma and betaARK1-associated PI3K activation. Furthermore, displacement of active PI3K from betaARK1 restores betaAR responsiveness in failing myocytes. ..
  87. Willets J, Taylor A, Shaw H, Konje J, Challiss R. Selective regulation of H1 histamine receptor signaling by G protein-coupled receptor kinase 2 in uterine smooth muscle cells. Mol Endocrinol. 2008;22:1893-907 pubmed publisher
    ..Dominant-negative GRK2, but not GRK5 or GRK6, prevented H(1) histamine receptor desensitization...
  88. Huang Z, Gao E, Chuprun J, Koch W. GRK2 in the heart: a GPCR kinase and beyond. Antioxid Redox Signal. 2014;21:2032-43 pubmed publisher
    ..and desensitization of ?-adrenergic receptors (?-AR) caused by G-protein-coupled receptor (GPCR) kinase 2 (GRK2) are prominent features of HF...