Grk2

Summary

Gene Symbol: Grk2
Description: G protein-coupled receptor kinase 2
Alias: Adrbk-1, Adrbk1, Bark-1, beta ARK, betaARK1, beta-adrenergic receptor kinase 1, adrenergic receptor kinase, beta 1, beta-AR kinase-1
Species: mouse
Products:     Grk2

Top Publications

  1. Sanchez Perez A, Kumar S, Cook D. GRK2 interacts with and phosphorylates Nedd4 and Nedd4-2. Biochem Biophys Res Commun. 2007;359:611-5 pubmed
    ..ENaC channels are maintained in the active state by G-protein-coupled receptor kinase 2 (GRK2), an enzyme implicated in the development of essential hypertension...
  2. Koch W, Rockman H, Samama P, Hamilton R, Bond R, Milano C, et al. Cardiac function in mice overexpressing the beta-adrenergic receptor kinase or a beta ARK inhibitor. Science. 1995;268:1350-3 pubmed
    ..mice were created with cardiac-specific overexpression of the beta-adrenergic receptor kinase-1 (beta ARK1) or a beta ARK inhibitor...
  3. Kleibeuker W, Jurado Pueyo M, Murga C, Eijkelkamp N, Mayor F, Heijnen C, et al. Physiological changes in GRK2 regulate CCL2-induced signaling to ERK1/2 and Akt but not to MEK1/2 and calcium. J Neurochem. 2008;104:979-92 pubmed
    G protein-coupled receptor (GPCR) kinase 2 (GRK2) regulates G protein-coupled receptor signaling via agonist-induced receptor phosphorylation and desensitization...
  4. Lymperopoulos A, Rengo G, Funakoshi H, Eckhart A, Koch W. Adrenal GRK2 upregulation mediates sympathetic overdrive in heart failure. Nat Med. 2007;13:315-23 pubmed
    ..in the adrenal gland, triggered by increased expression and activity of G protein-coupled receptor kinase 2 (GRK2)...
  5. Jiménez Sainz M, Murga C, Kavelaars A, Jurado Pueyo M, Krakstad B, Heijnen C, et al. G protein-coupled receptor kinase 2 negatively regulates chemokine signaling at a level downstream from G protein subunits. Mol Biol Cell. 2006;17:25-31 pubmed
    The G protein-coupled receptor kinase 2 (GRK2) phosphorylates and desensitizes ligand-activated G protein-coupled-receptors. Here, evidence is shown for a novel role of GRK2 in regulating chemokine-mediated signals...
  6. Chen M, Sato P, Chuprun J, Peroutka R, Otis N, Ibetti J, et al. Prodeath signaling of G protein-coupled receptor kinase 2 in cardiac myocytes after ischemic stress occurs via extracellular signal-regulated kinase-dependent heat shock protein 90-mediated mitochondrial targeting. Circ Res. 2013;112:1121-34 pubmed publisher
    G protein-coupled receptor kinase 2 (GRK2) is abundantly expressed in the heart, and its expression and activity are increased in injured or stressed myocardium. This upregulation has been shown to be pathological...
  7. Anis Y, Leshem O, Reuveni H, Wexler I, Ben Sasson R, Yahalom B, et al. Antidiabetic effect of novel modulating peptides of G-protein-coupled kinase in experimental models of diabetes. Diabetologia. 2004;47:1232-1244 pubmed publisher
    ..Our aim was to examine whether small peptides derived from the catalytic domain of GRK2 and -3 would ameliorate Type 2 diabetes in three separate animal models of diabetes...
  8. Raake P, Vinge L, Gao E, Boucher M, Rengo G, Chen X, et al. G protein-coupled receptor kinase 2 ablation in cardiac myocytes before or after myocardial infarction prevents heart failure. Circ Res. 2008;103:413-22 pubmed publisher
    ..Preventing GRK2 translocation to activated betaAR with a GRK2-derived peptide that binds G(beta)gamma (betaARKct) has benefited ..
  9. Matkovich S, Diwan A, Klanke J, Hammer D, Marreez Y, Odley A, et al. Cardiac-specific ablation of G-protein receptor kinase 2 redefines its roles in heart development and beta-adrenergic signaling. Circ Res. 2006;99:996-1003 pubmed
    G-protein receptor kinase 2 (GRK2) is 1 of 7 mammalian GRKs that phosphorylate ligand-bound 7-transmembrane receptors, causing receptor uncoupling from G proteins and potentially activating non-G-protein signaling pathways...

More Information

Publications92

  1. Jaber M, Koch W, Rockman H, Smith B, Bond R, Sulik K, et al. Essential role of beta-adrenergic receptor kinase 1 in cardiac development and function. Proc Natl Acad Sci U S A. 1996;93:12974-9 pubmed
  2. Usui I, Imamura T, Satoh H, Huang J, Babendure J, Hupfeld C, et al. GRK2 is an endogenous protein inhibitor of the insulin signaling pathway for glucose transport stimulation. EMBO J. 2004;23:2821-9 pubmed
    ..b>GRK2 contains a regulator of G protein signaling (RGS) domain with specificity for Galphaq/11...
  3. Rockman H, Choi D, Akhter S, Jaber M, Giros B, Lefkowitz R, et al. Control of myocardial contractile function by the level of beta-adrenergic receptor kinase 1 in gene-targeted mice. J Biol Chem. 1998;273:18180-4 pubmed
    We studied the effect of alterations in the level of myocardial beta-adrenergic receptor kinase betaARK1) in two types of genetically altered mice...
  4. Shahid G, Hussain T. GRK2 negatively regulates glycogen synthesis in mouse liver FL83B cells. J Biol Chem. 2007;282:20612-20 pubmed
    ..The present study was designed to test the hypothesis that GRK2 negatively regulates IR signaling...
  5. 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...
  6. Deford Watts L, Young J, Pitcher L, van Oers N. The membrane-proximal portion of CD3 epsilon associates with the serine/threonine kinase GRK2. J Biol Chem. 2007;282:16126-34 pubmed
    ..Mass spectrometry analysis of CD3 epsilon-associated proteins identified G protein-coupled receptor kinase 2 (GRK2) as a candidate Ser/Thr kinase...
  7. Chang J, Milligan S, Li Y, Chew C, Wiggs J, Copeland N, et al. Mammalian homolog of Drosophila retinal degeneration B rescues the mutant fly phenotype. J Neurosci. 1997;17:5881-90 pubmed
    ..These results suggest the existence of similarities between the invertebrate and mammalian retina that were not previously appreciated and also identify mrdgB as a candidate gene for retinal diseases that map to 11q13.1. ..
  8. Nijboer C, Heijnen C, Degos V, Willemen H, Gressens P, Kavelaars A. Astrocyte GRK2 as a novel regulator of glutamate transport and brain damage. Neurobiol Dis. 2013;54:206-15 pubmed publisher
    G protein-coupled receptor (GPCR) kinase 2 (GRK2) regulates cellular signaling via desensitization of GPCRs and by direct interaction with intracellular signaling molecules...
  9. Tsukada S, Simon M, Witte O, Katz A. Binding of beta gamma subunits of heterotrimeric G proteins to the PH domain of Bruton tyrosine kinase. Proc Natl Acad Sci U S A. 1994;91:11256-60 pubmed
    ..The interaction of Btk with beta gamma suggests the existence of a unique connection between cytoplasmic tyrosine kinases and G proteins in cellular signal transduction. ..
  10. 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...
  11. Neill J, Musgrove L, Sellers J, Duck L. Identification by polymerase chain reaction of the G protein-coupled receptor kinases expressed in the mouse gonadotropic alpha T3-1 cell line. Endocrinology. 1996;137:3942-7 pubmed
    ..were receptor kinases based on high nucleotide identities of 85-100% and amino acid identities of 97-100% with rat GRK2 and 3, and with human GRK6...
  12. Curcio A, Noma T, Naga Prasad S, Wolf M, Lemaire A, Perrino C, et al. Competitive displacement of phosphoinositide 3-kinase from beta-adrenergic receptor kinase-1 improves postinfarction adverse myocardial remodeling. Am J Physiol Heart Circ Physiol. 2006;291:H1754-60 pubmed
    ..Together, these results demonstrate that adverse remodeling of the ventricle after MI can be attenuated by a strategy that prevents recruitment of PI3K to the plasma membrane and restores normal beta-AR function. ..
  13. Rakesh K, Yoo B, Kim I, Salazar N, Kim K, Rockman H. beta-Arrestin-biased agonism of the angiotensin receptor induced by mechanical stress. Sci Signal. 2010;3:ra46 pubmed publisher
    ..These data show that the heart responds to acute increases in mechanical stress by activating beta-arrestin-mediated cell survival signals. ..
  14. Fan X, Zhang J, Zhang X, Yue W, Ma L. Acute and chronic morphine treatments and morphine withdrawal differentially regulate GRK2 and GRK5 gene expression in rat brain. Neuropharmacology. 2002;43:809-16 pubmed
    ..study investigated the potential regulatory effects of acute and chronic morphine administration and withdrawal on GRK2 and GRK5 gene expression in rat brain...
  15. Vroon A, Kavelaars A, Limmroth V, Lombardi M, Goebel M, van Dam A, et al. G protein-coupled receptor kinase 2 in multiple sclerosis and experimental autoimmune encephalomyelitis. J Immunol. 2005;174:4400-6 pubmed
    ..leukocytes from patients with active relapsing-remitting multiple sclerosis (MS) or with secondary progressive MS, GRK2 levels are significantly reduced...
  16. Kandasamy K, Choudhury S, Singh V, Addison M, Darzi S, Kasa J, et al. Erythropoietin Reverses Sepsis-Induced Vasoplegia to Norepinephrine Through Preservation of α1D-Adrenoceptor mRNA Expression and Inhibition of GRK2-Mediated Desensitization in Mouse Aorta. J Cardiovasc Pharmacol Ther. 2016;21:100-13 pubmed publisher
    ..nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), G protein-coupled receptor kinase 2 (GRK2), and α1D adrenoceptor messenger RNA (mRNA)/protein expression...
  17. Nijboer C, Kavelaars A, Vroon A, Groenendaal F, van Bel F, Heijnen C. Low endogenous G-protein-coupled receptor kinase 2 sensitizes the immature brain to hypoxia-ischemia-induced gray and white matter damage. J Neurosci. 2008;28:3324-32 pubmed publisher
    ..GPCR-kinase 2 (GRK2) protects these receptors against overstimulation by inducing desensitization...
  18. Verma V, Hasbi A, O Dowd B, George S. Dopamine D1-D2 receptor Heteromer-mediated calcium release is desensitized by D1 receptor occupancy with or without signal activation: dual functional regulation by G protein-coupled receptor kinase 2. J Biol Chem. 2010;285:35092-103 pubmed publisher
    ..studies indicated an agonist-induced physical association between the D1-D2 receptor heteromeric complex and GRK2. Increased expression of GRK2 led to a decrease in the calcium signal with or without prior exposure to either SKF ..
  19. Fernandes M, Lespinasse F, Rotomondo F, Poirier C, Guenet J, Gaudray P, et al. Comparative mapping of two adjacent regions of MMU19 with their human counterpart on HSA11q13. Cytogenet Cell Genet. 1998;81:237-46 pubmed
    ..5-Mb region. Strikingly, the 0.5-Mb region has a similar size in human but gene order is shuffled. The overall comparative map shows that these two regions are inverted on MMU19 when compared with HSA11q13. ..
  20. Pal K, Hwang S, Somatilaka B, Badgandi H, Jackson P, DeFea K, et al. Smoothened determines ?-arrestin-mediated removal of the G protein-coupled receptor Gpr161 from the primary cilium. J Cell Biol. 2016;212:861-75 pubmed publisher
    ..step involves ?-arrestin recruitment by the signaling competent receptor, which is facilitated by the GPCR kinase Grk2. An essential factor here is the ciliary trafficking and activation of Smoothened, which by increasing Gpr161-?-..
  21. Patial S, Saini Y, Parvataneni S, Appledorn D, Dorn G, LaPres J, et al. Myeloid-specific GPCR kinase-2 negatively regulates NF-?B1p105-ERK pathway and limits endotoxemic shock in mice. J Cell Physiol. 2011;226:627-37 pubmed publisher
    G-protein-coupled receptor kinase 2 (GRK2) is a member of a kinase family originally discovered for its role in the phosphorylation and desensitization of G-protein-coupled receptors...
  22. Sexton T, Van Gelder R. G-Protein Coupled Receptor Kinase 2 Minimally Regulates Melanopsin Activity in Intrinsically Photosensitive Retinal Ganglion Cells. PLoS ONE. 2015;10:e0128690 pubmed publisher
    ..Recent evidence from in vitro experiments suggests that the G-protein coupled receptor kinase 2 (GRK2) phosphorylates melanopsin and reduces its activity following light exposure...
  23. Vila Bedmar R, Cruces Sande M, Lucas E, Willemen H, Heijnen C, Kavelaars A, et al. Reversal of diet-induced obesity and insulin resistance by inducible genetic ablation of GRK2. Sci Signal. 2015;8:ra73 pubmed publisher
    ..G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor kinase 2 (GRK2) integrates several signal transduction pathways and is emerging as a physiologically relevant inhibitor of insulin ..
  24. Dal Secco D, DalBó S, Lautherbach N, Gava F, Celes M, Benedet P, et al. Cardiac hyporesponsiveness in severe sepsis is associated with nitric oxide-dependent activation of G protein receptor kinase. Am J Physiol Heart Circ Physiol. 2017;313:H149-H163 pubmed publisher
    G protein-coupled receptor kinase isoform 2 (GRK2) has a critical role in physiological and pharmacological responses to endogenous and exogenous substances...
  25. Rivas V, Carmona R, Muñoz Chápuli R, Mendiola M, Nogués L, Reglero C, et al. Developmental and tumoral vascularization is regulated by G protein-coupled receptor kinase 2. J Clin Invest. 2013;123:4714-30 pubmed publisher
    ..Using an in vivo neovascularization model, we identified G protein-coupled receptor kinase 2 (GRK2) as a key angiogenesis regulator...
  26. Urs N, Gee S, Pack T, McCorvy J, Evron T, Snyder J, et al. Distinct cortical and striatal actions of a β-arrestin-biased dopamine D2 receptor ligand reveal unique antipsychotic-like properties. Proc Natl Acad Sci U S A. 2016;113:E8178-E8186 pubmed
    ..Therefore, we propose that βarr2-biased D2R ligands that exert region-selective actions could provide a path to develop more effective antipsychotic therapies. ..
  27. Beraldo F, Soares I, Gonçalves D, Fan J, Thomas A, Santos T, et al. Stress-inducible phosphoprotein 1 has unique cochaperone activity during development and regulates cellular response to ischemia via the prion protein. FASEB J. 2013;27:3594-607 pubmed publisher
    ..Interesting, extracellular STI1 prevented ischemia-mediated neuronal death in a prion protein-dependent way. Our study reveals essential roles for intracellular and extracellular STI1 in cellular resilience. ..
  28. Otten J, de Jager S, Kavelaars A, Seijkens T, Bot I, Wijnands E, et al. Hematopoietic G-protein-coupled receptor kinase 2 deficiency decreases atherosclerotic lesion formation in LDL receptor-knockout mice. FASEB J. 2013;27:265-76 pubmed publisher
    ..In this study, we analyzed the effect of hematopoietic deficiency of a potent regulator kinase of chemotaxis (GRK2) on atherogenesis...
  29. Lafarga V, Aymerich I, Tapia O, Mayor F, Penela P. A novel GRK2/HDAC6 interaction modulates cell spreading and motility. EMBO J. 2012;31:856-69 pubmed publisher
    ..We identify G protein-coupled receptor kinase 2 (GRK2) as a key novel stimulator of HDAC6...
  30. Dang V, Napier I, Christie M. Two distinct mechanisms mediate acute mu-opioid receptor desensitization in native neurons. J Neurosci. 2009;29:3322-7 pubmed publisher
    ..The rate and extent of MOR desensitization were unaffected by beta(arr)-2 knock-out. Disruption of GRK2 function via inhibitory peptide introduced directly into neurons also failed to affect desensitization in wild type ..
  31. Esposito G, Santana L, Dilly K, Cruz J, Mao L, Lederer W, et al. Cellular and functional defects in a mouse model of heart failure. Am J Physiol Heart Circ Physiol. 2000;279:H3101-12 pubmed
    ..express a cardiac-targeted transgene, which blocks the function of beta-adrenergic receptor (beta-AR) kinase-1 (betaARK1). These data suggest that, despite the persistent stimulus to develop heart failure in MLP(-/-) mice (i.e...
  32. Woodall M, Woodall B, Gao E, Yuan A, Koch W. Cardiac Fibroblast GRK2 Deletion Enhances Contractility and Remodeling Following Ischemia/Reperfusion Injury. Circ Res. 2016;119:1116-1127 pubmed
    G protein-coupled receptor kinase 2 (GRK2) is an important molecule upregulated after myocardial injury and during heart failure...
  33. Wang Q, Zhao J, Brady A, Feng J, Allen P, Lefkowitz R, et al. Spinophilin blocks arrestin actions in vitro and in vivo at G protein-coupled receptors. Science. 2004;304:1940-4 pubmed
    ..Through blocking G protein receptor kinase 2 (GRK2) association with receptor-Gbetagamma complexes, spinophilin reduces arrestin-stabilized receptor phosphorylation, ..
  34. Cohn H, Harris D, Pesant S, Pfeiffer M, Zhou R, Koch W, et al. Inhibition of vascular smooth muscle G protein-coupled receptor kinase 2 enhances alpha1D-adrenergic receptor constriction. Am J Physiol Heart Circ Physiol. 2008;295:H1695-704 pubmed publisher
    G protein-coupled receptor kinase 2 (GRK2) is a serine/theorinine kinase that phosphorylates and desensitizes agonist-bound G protein-coupled receptors...
  35. Wang Y, Gao E, Lau W, Wang Y, Liu G, Li J, et al. G-protein-coupled receptor kinase 2-mediated desensitization of adiponectin receptor 1 in failing heart. Circulation. 2015;131:1392-404 pubmed publisher
    ..Cardiac-specific GRK2 knockout virtually abolished post-MI AdipoR1 phosphorylation, whereas virus-mediated GRK2 overexpression ..
  36. Taguchi K, Matsumoto T, Kamata K, Kobayashi T. Inhibitor of G protein-coupled receptor kinase 2 normalizes vascular endothelial function in type 2 diabetic mice by improving ?-arrestin 2 translocation and ameliorating Akt/eNOS signal dysfunction. Endocrinology. 2012;153:2985-96 pubmed publisher
    ..NO synthase (eNOS) activation is known to be negatively regulated by G protein-coupled receptor kinase 2 (GRK2), it is unclear whether the GRK2 inhibitor would have therapeutic effects...
  37. Fu X, Koller S, Abd Alla J, Quitterer U. Inhibition of G-protein-coupled receptor kinase 2 (GRK2) triggers the growth-promoting mitogen-activated protein kinase (MAPK) pathway. J Biol Chem. 2013;288:7738-55 pubmed publisher
    Inhibition of G-protein-coupled receptor kinase 2 (GRK2) is an emerging treatment option for heart failure...
  38. Singhmar P, Huo X, Eijkelkamp N, Berciano S, Baameur F, Mei F, et al. Critical role for Epac1 in inflammatory pain controlled by GRK2-mediated phosphorylation of Epac1. Proc Natl Acad Sci U S A. 2016;113:3036-41 pubmed publisher
    ..in which direct phosphorylation of the exchange protein directly activated by cAMP 1 (EPAC1) by G protein kinase 2 (GRK2) suppresses Epac1-to-Rap1 signaling, thereby inhibiting persistent inflammatory pain...
  39. Lucas E, Jurado Pueyo M, Fortuño M, Fernández Veledo S, Vila Bedmar R, Jiménez Borreguero L, et al. Downregulation of G protein-coupled receptor kinase 2 levels enhances cardiac insulin sensitivity and switches on cardioprotective gene expression patterns. Biochim Biophys Acta. 2014;1842:2448-56 pubmed publisher
    G protein-coupled receptor kinase 2 (GRK2) has recently emerged as a negative modulator of insulin signaling. GRK2 downregulation improves insulin sensitivity and prevents systemic insulin resistance...
  40. Eijkelkamp N, Heijnen C, Willemen H, Deumens R, Joosten E, Kleibeuker W, et al. GRK2: a novel cell-specific regulator of severity and duration of inflammatory pain. J Neurosci. 2010;30:2138-49 pubmed publisher
    ..b>GRK2 regulates cellular signaling by promoting G-protein-coupled receptor (GPCR) desensitization and direct interaction ..
  41. Avendaño M, Lucas E, Jurado Pueyo M, Martinez Revelles S, Vila Bedmar R, Mayor F, et al. Increased nitric oxide bioavailability in adult GRK2 hemizygous mice protects against angiotensin II-induced hypertension. Hypertension. 2014;63:369-75 pubmed publisher
    G protein-coupled receptor kinase 2 (GRK2) is a ubiquitous serine/threonine protein kinase able to phosphorylate and desensitize the active form of several G protein-coupled receptors...
  42. Tutunea Fatan E, Caetano F, Gros R, Ferguson S. GRK2 targeted knock-down results in spontaneous hypertension, and altered vascular GPCR signaling. J Biol Chem. 2015;290:5141-55 pubmed publisher
    ..b>GRK2 expression is increased in hypertension and this facilitates the development of the hypertensive state by ..
  43. Benovic J, Strasser R, Caron M, Lefkowitz R. Beta-adrenergic receptor kinase: identification of a novel protein kinase that phosphorylates the agonist-occupied form of the receptor. Proc Natl Acad Sci U S A. 1986;83:2797-801 pubmed
    ..It also suggests a general mechanism for regulation of receptor function in which only the agonist-occupied or "active" form of the receptor is a substrate for enzymes inducing covalent modification. ..
  44. 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...
  45. Penela P, Ribas C, Aymerich I, Eijkelkamp N, Barreiro O, Heijnen C, et al. G protein-coupled receptor kinase 2 positively regulates epithelial cell migration. EMBO J. 2008;27:1206-18 pubmed publisher
    ..We find that increased levels of G protein-coupled receptor kinase 2 (GRK2), a key player in GPCR regulation, potentiate migration of epithelial cells towards fibronectin, whereas such ..
  46. Kleibeuker W, Gabay E, Kavelaars A, Zijlstra J, Wolf G, Ziv N, et al. IL-1 beta signaling is required for mechanical allodynia induced by nerve injury and for the ensuing reduction in spinal cord neuronal GRK2. Brain Behav Immun. 2008;22:200-8 pubmed
    ..GPCR kinase 2 (GRK2) regulates agonist-induced desensitization and signaling of multiple GPCRs and interacts with downstream molecules ..
  47. Ozaki S, Narita M, Iino M, Miyoshi K, Suzuki T. Suppression of the morphine-induced rewarding effect and G-protein activation in the lower midbrain following nerve injury in the mouse: involvement of G-protein-coupled receptor kinase 2. Neuroscience. 2003;116:89-97 pubmed
  48. Vila Bedmar R, Garcia Guerra L, Nieto Vazquez I, Mayor F, Lorenzo M, Murga C, et al. GRK2 contribution to the regulation of energy expenditure and brown fat function. FASEB J. 2012;26:3503-14 pubmed publisher
    ..Previous studies in our laboratory have revealed that down-regulation of GRK2 decreases age-related adiposity, but the physiological and molecular mechanisms underlying this outcome remain ..
  49. Daigle T, Ferris M, Gainetdinov R, Sotnikova T, Urs N, Jones S, et al. Selective deletion of GRK2 alters psychostimulant-induced behaviors and dopamine neurotransmission. Neuropsychopharmacology. 2014;39:2450-62 pubmed publisher
    b>GRK2 is a G protein-coupled receptor kinase (GRK) that is broadly expressed and is known to regulate diverse types of receptors...
  50. Tarrant T, Rampersad R, Esserman D, Rothlein L, Liu P, Premont R, et al. Granulocyte chemotaxis and disease expression are differentially regulated by GRK subtype in an acute inflammatory arthritis model (K/BxN). Clin Immunol. 2008;129:115-22 pubmed publisher
    ..Clinical, histologic, and cytokine responses in GRK6-/-, GRK5-/-, GRK2+/-, and wildtype mice were evaluated using K/BxN serum transfer...
  51. Taguchi K, Kobayashi T, Takenouchi Y, Matsumoto T, Kamata K. Angiotensin II causes endothelial dysfunction via the GRK2/Akt/eNOS pathway in aortas from a murine type 2 diabetic model. Pharmacol Res. 2011;64:535-46 pubmed publisher
    ..Relaxations and NO productions were measured in isolated aortas. G-protein coupled receptor kinase 2 (GRK2) protein levels and activities in the Akt/eNOS signaling-pathway were mainly assayed by Western blotting...
  52. Cho M, Rao M, Koch W, Thomas S, Palmiter R, Rockman H. Enhanced contractility and decreased beta-adrenergic receptor kinase-1 in mice lacking endogenous norepinephrine and epinephrine. Circulation. 1999;99:2702-7 pubmed
    ..human dilated cardiomyopathy, a process mediated in part by increased levels of beta-adrenergic receptor kinase (betaARK1)...
  53. Koch W, Rockman H. Exploring the role of the beta-adrenergic receptor kinase in cardiac disease using gene-targeted mice. Trends Cardiovasc Med. 1999;9:77-81 pubmed
    ..Interrupting this process may provide novel therapeutic strategies in the treatment of human heart failure. ..
  54. Sato P, Chuprun J, Ibetti J, Cannavo A, Drosatos K, Elrod J, et al. GRK2 compromises cardiomyocyte mitochondrial function by diminishing fatty acid-mediated oxygen consumption and increasing superoxide levels. J Mol Cell Cardiol. 2015;89:360-4 pubmed publisher
    The G protein-coupled receptor kinase-2 (GRK2) is upregulated in the injured heart and contributes to heart failure pathogenesis...
  55. Garcia Guerra L, Nieto Vazquez I, Vila Bedmar R, Jurado Pueyo M, Zalba G, Diez J, et al. G protein-coupled receptor kinase 2 plays a relevant role in insulin resistance and obesity. Diabetes. 2010;59:2407-17 pubmed publisher
    ..transduction in these syndromes, we set out to explore the possible role that G protein-coupled receptor kinase 2 (GRK2), first identified as a G protein-coupled receptor regulator, could have as a modulator of insulin responses...
  56. Harding V, Jones L, Lefkowitz R, Koch W, Rockman H. Cardiac beta ARK1 inhibition prolongs survival and augments beta blocker therapy in a mouse model of severe heart failure. Proc Natl Acad Sci U S A. 2001;98:5809-14 pubmed
    ..by abnormalities in beta-adrenergic receptor (betaAR) signaling, including increased levels of betaAR kinase 1 (betaARK1), which seems critical to the pathogenesis of the disease...
  57. Chen X, Zhao S, Xia Y, Xiong Z, Li Y, Tao L, et al. G protein coupled receptor kinase-2 upregulation causes ?-opioid receptor desensitization in diabetic heart. Biochem Biophys Res Commun. 2017;482:658-664 pubmed publisher
    ..HG) caused obvious KOR downregulation, accompanied by an upregulation of G protein coupled receptor kinase-2 (GRK2). We found that HG exposure increased the interaction between GRK2 and KOR...
  58. Kleibeuker W, Ledeboer A, Eijkelkamp N, Watkins L, Maier S, Zijlstra J, et al. A role for G protein-coupled receptor kinase 2 in mechanical allodynia. Eur J Neurosci. 2007;25:1696-704 pubmed
    ..Low intracellular GRK2 levels are associated with increased receptor signalling...
  59. Ciccarelli M, Chuprun J, Rengo G, Gao E, Wei Z, Peroutka R, et al. G protein-coupled receptor kinase 2 activity impairs cardiac glucose uptake and promotes insulin resistance after myocardial ischemia. Circulation. 2011;123:1953-62 pubmed publisher
    ..heart failure is a signaling abnormality that leads to the upregulation of G protein-coupled receptor kinase 2 (GRK2), which is pathological in the myocyte during disease progression in part owing to uncoupling of the ?-adrenergic ..
  60. Huang P, Lu X, Yuan B, Liu T, Dai L, Liu Y, et al. Astragaloside IV alleviates E. coli-caused peritonitis via upregulation of neutrophil influx to the site of infection. Int Immunopharmacol. 2016;39:377-382 pubmed publisher
    ..suppression of CXCR2 on neutrophils by inhibiting the expression of G protein-coupled receptor kinase-2 (GRK2), an agonist that regulates desensitization and internalization of chemokine receptors...
  61. Rajagopal K, Whalen E, Violin J, Stiber J, Rosenberg P, Premont R, et al. Beta-arrestin2-mediated inotropic effects of the angiotensin II type 1A receptor in isolated cardiac myocytes. Proc Natl Acad Sci U S A. 2006;103:16284-9 pubmed
    ..Cardiomyocytes from GRK2 heterozygous knockout mice (GRK2(+/-)) exhibited augmented responses to SII in comparison to ANG, whereas those ..
  62. Evron T, Philipp M, Lu J, Meloni A, Burkhalter M, Chen W, et al. Growth Arrest Specific 8 (Gas8) and G protein-coupled receptor kinase 2 (GRK2) cooperate in the control of Smoothened signaling. J Biol Chem. 2011;286:27676-86 pubmed publisher
    ..Smoothened (Smo) undergoes dynamic intracellular trafficking modulated by the microtubule associated kinase GRK2 and recruitment of ?-arrestin...
  63. Weissman J, Ma J, Essex A, Gao Y, Burstein E. G-protein-coupled receptor-mediated activation of rap GTPases: characterization of a novel Galphai regulated pathway. Oncogene. 2004;23:241-9 pubmed
    ..A constitutively active mutant of Galphai2 also mediated Ras/rap-dependent responses. These data indicate that GPCRs coupled to pertussis-toxin-sensitive G-proteins activate Rap through a Galpha subunit, C3G, and Src-dependent pathway. ..
  64. Sherrill J, Miller W. G protein-coupled receptor (GPCR) kinase 2 regulates agonist-independent Gq/11 signaling from the mouse cytomegalovirus GPCR M33. J Biol Chem. 2006;281:39796-805 pubmed
    ..Our data also show that GRK2 is a potent regulator of M33-induced G(q/11) signaling through its ability to phosphorylate M33 and sequester ..
  65. Willemen H, Eijkelkamp N, Wang H, Dantzer R, Dorn G, Kelley K, et al. Microglial/macrophage GRK2 determines duration of peripheral IL-1beta-induced hyperalgesia: contribution of spinal cord CX3CR1, p38 and IL-1 signaling. Pain. 2010;150:550-60 pubmed publisher
    ..Recently, we reported that GRK2(+/-) mice with a approximately 50% reduction of GRK2 develop prolonged hyperalgesia following a single intraplantar ..
  66. Zhao Z, Lee R, Pusapati G, Iyu A, Rohatgi R, Ingham P. An essential role for Grk2 in Hedgehog signalling downstream of Smoothened. EMBO Rep. 2016;17:739-52 pubmed publisher
    The G-protein-coupled receptor kinase 2 (adrbk2/GRK2) has been implicated in vertebrate Hedgehog (Hh) signalling based on the effects of its transient knock-down in mammalian cells and zebrafish embryos...
  67. Woodall B, Woodall M, Luongo T, Grisanti L, Tilley D, Elrod J, et al. Skeletal Muscle-specific G Protein-coupled Receptor Kinase 2 Ablation Alters Isolated Skeletal Muscle Mechanics and Enhances Clenbuterol-stimulated Hypertrophy. J Biol Chem. 2016;291:21913-21924 pubmed
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    ..Here we show that a 2-fold overexpression of GRK2 leads to the attenuation of endogenous mGluR5-mediated inositol phosphate (InsP) formation in striatal neurons and ..
  69. Nijboer C, Heijnen C, Willemen H, Groenendaal F, Dorn G, van Bel F, et al. Cell-specific roles of GRK2 in onset and severity of hypoxic-ischemic brain damage in neonatal mice. Brain Behav Immun. 2010;24:420-6 pubmed publisher
    The ubiquitously expressed kinase GRK2 protects against cellular overstimulation by desensitizing G protein-coupled receptors and regulating intracellular signaling...
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    ..We also show that LPS, through p38 MAPK signaling, induces phosphorylation of GRK2 at serine 670, which, in turn, suppresses GRK2 translocation to the membrane, thereby preventing GRK2-initiated ..
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    G-protein-coupled receptor kinase 2 (GRK2) is a primary regulator of ?-adrenergic signaling in the heart...
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    ..G protein-coupled receptor kinase 2 (GRK2) plays a central role in G protein-coupled receptor regulation...
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    ..These findings will potentially aid in the design of novel therapies for reproductive disorders associated with myometrial defects. ..
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    G protein-coupled receptor kinase 2 (GRK2) plays a fundamental role in the regulation of G protein-coupled receptors (GPCRs), and changes in GRK2 expression levels can have an important impact on cell functions...
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    ..G protein-coupled receptor kinase 2 (GRK2) is an ubiquitous kinase able to desensitize the active form of several G protein-coupled receptors (GPCR) and is ..
  77. Ciccarelli M, Sorriento D, Franco A, Fusco A, Del Giudice C, Annunziata R, et al. Endothelial G protein-coupled receptor kinase 2 regulates vascular homeostasis through the control of free radical oxygen species. Arterioscler Thromb Vasc Biol. 2013;33:2415-24 pubmed publisher
    The role of endothelial G protein-coupled receptor kinase 2 (GRK2) was investigated in mice with selective deletion of the kinase in the endothelium (Tie2-CRE/GRK2(fl/fl))...
  78. Patial S, Luo J, Porter K, Benovic J, Parameswaran N. G-protein-coupled-receptor kinases mediate TNF?-induced NF?B signalling via direct interaction with and phosphorylation of I?B?. Biochem J. 2009;425:169-78 pubmed publisher
    ..We demonstrate here that G-protein coupled receptor kinase-2 and 5 (GRK2 and 5) regulate TNF?-induced NF?B signaling in Raw264.7 macrophages...
  79. Wang Y, De Arcangelis V, Gao X, Ramani B, Jung Y, Xiang Y. Norepinephrine- and epinephrine-induced distinct beta2-adrenoceptor signaling is dictated by GRK2 phosphorylation in cardiomyocytes. J Biol Chem. 2008;283:1799-807 pubmed
    ..showed that the Epi-activated beta(2)AR underwent a rapid phosphorylation by G protein-coupled receptor kinase 2 (GRK2) and subsequent dephosphorylation on serine residues 355 and 356, which was critical for sufficient receptor ..
  80. del Rey A, Renigunta V, Dalpke A, Leipziger J, Matos J, Robaye B, et al. Knock-out mice reveal the contributions of P2Y and P2X receptors to nucleotide-induced Ca2+ signaling in macrophages. J Biol Chem. 2006;281:35147-55 pubmed
    ..This apparent receptor desensitization persisted in GRK2+/- and GRK6-/- macrophages and after inhibition of candidate kinases protein kinase C and calmodulin-dependent ..
  81. Dawson T, Arriza J, Jaworsky D, Borisy F, Attramadal H, Lefkowitz R, et al. Beta-adrenergic receptor kinase-2 and beta-arrestin-2 as mediators of odorant-induced desensitization. Science. 1993;259:825-9 pubmed
    beta-Adrenergic receptor kinase (beta ARK) and beta-arrestin function in the homologous or agonist-activated desensitization of G protein-coupled receptors...
  82. Schlegel P, Reinkober J, Meinhardt E, Tscheschner H, Gao E, Schumacher S, et al. G protein-coupled receptor kinase 2 promotes cardiac hypertrophy. PLoS ONE. 2017;12:e0182110 pubmed publisher
    The increase in protein activity and upregulation of G-protein coupled receptor kinase 2 (GRK2) is a hallmark of cardiac stress and heart failure...
  83. Jones B, Hinkle P. Beta-arrestin mediates desensitization and internalization but does not affect dephosphorylation of the thyrotropin-releasing hormone receptor. J Biol Chem. 2005;280:38346-54 pubmed
    ..Overexpression of dominant negative G protein-coupled receptor kinase-2 (GRK2), however, retarded receptor phosphorylation...