Trends in Cardiovascular Medicine
Volume 16, Issue 5 , Pages 169-177 , July 2006

Role of G-Protein-Coupled Receptor Kinase 2 in the Heart—Do Regulatory Mechanisms Open Novel Therapeutic Perspectives?

References 

  1. Cant SH, Pitcher JA. 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;16:3088–3099
  2. Carman CV, Lisanti MP, Benovic JL. Regulation of G protein-coupled receptor kinases by caveolin. J Biol Chem. 1999;274:8858–8864
  3. Carman CV, Parent JL, Day PW, et al. Selective regulation of Galpha(q/11) by an RGS domain in the G protein-coupled receptor kinase, GRK2. J Biol Chem. 1999;274:34483–34492
  4. Cong M, Perry SJ, Lin FT, 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;276:15192–15199
  5. DebBurman SK, Ptasienski J, Benovic JL, Hosey MM. G protein-coupled receptor kinase GRK2 is a phospholipid-dependent enzyme that can be conditionally activated by G protein betagamma subunits. J Biol Chem. 1996;271:22552–22562
  6. DebBurman SK, Ptasienski J, Boetticher E, et al. Lipid-mediated regulation of G protein-coupled receptor kinases 2 and 3. J Biol Chem. 1995;270:5742–5747
  7. De Blasi A, Parruti G, Sallese M. Regulation of G protein-coupled receptor kinase subtypes in activated T lymphocytes. Selective increase of beta-adrenergic receptor kinase 1 and 2. J Clin Invest. 1995;95:203–210
  8. Dinudom A, Fotia AB, Lefkowitz RJ, et al. The kinase Grk2 regulates Nedd4/Nedd4-2-dependent control of epithelial Na+ channels. Proc Natl Acad Sci U S A. 2004;101:11886–11890
  9. Daaka Y, Luttrell LM, Lefkowitz RJ. Switching of the coupling of the beta2-adrenergic receptor to different G proteins by protein kinase A. Nature. 1997;390:88–91
  10. Daaka Y, Pitcher JA, Richardson M, et al. Receptor and G betagamma isoform-specific interactions with G protein-coupled receptor kinases. Proc Natl Acad Sci U S A. 1997;94:2180–2185
  11. Eichmann T, Lorenz K, Hoffmann M, et al. The amino-terminal domain of G-protein-coupled receptor kinase 2 is a regulatory Gbeta gamma binding site. J Biol Chem. 2003;278:8052–8057
  12. Elorza A, Sarnago S, Mayor F. Agonist-dependent modulation of G protein-coupled receptor kinase 2 by mitogen-activated protein kinases. Mol Pharmacol. 2000;57:778–783
  13. Elorza A, Penela P, Sarnago S, Mayor F. MAPK-dependent degradation of G protein-coupled receptor kinase 2. J Biol Chem. 2003;278:29164–29173
  14. Feldman RD. Deactivation of vasodilator responses by GRK2 overexpression: a mechanism or the mechanism for hypertension?. Mol Pharmacol. 2002;61:707–709
  15. Freedman NJ, Kim LK, Murray JP, 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;277:48261–48269
  16. Freeman JL, Pitcher JA, Li X, et al. alpha-Actinin is a potent regulator of G protein-coupled receptor kinase activity and substrate specificity in vitro. FEBS Lett. 2000;473:280–284
  17. Freeman JL, Gonzalo P, Pitcher JA, et al. Beta 2-adrenergic receptor stimulated, G protein-coupled receptor kinase 2 mediated, phosphorylation of ribosomal protein P2. Biochemistry. 2002;41:12850–12857
  18. Gao J, Li J, Chen Y, Ma L. Activation of tyrosine kinase of EGFR induces Gbetagamma-dependent GRK-EGFR complex formation. FEBS Lett. 2005;579:122–126
  19. Harding VB, Jones LR, Lefkowitz RJ, et al. 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;98:5809–5814
  20. Iaccarino G, Tomhave ED, Lefkowitz RJ, Koch WJ. Reciprocal in vivo regulation of myocardial G protein-coupled receptor kinase expression by beta-adrenergic receptor stimulation and blockade. Circulation. 1998;98:1783–1789
  21. Inglese J, Freedman NJ, Koch WJ, Lefkowitz RJ. Structure and mechanism of the G protein-coupled receptor kinases. J Biol Chem. 1993;268:23735–23738
  22. Jo SH, Leblais V, Wang PH, et al. Phosphatidylinositol 3-kinase functionally compartmentalizes the concurrent G(s) signaling during beta2-adrenergic stimulation. Circ Res. 2002;91:46–53
  23. Kabbani N, Negyessy L, Lin R, et al. Interaction with neuronal calcium sensor NCS-1 mediates desensitization of the D2 dopamine receptor. J Neurosci. 2002;22:8476–8486
  24. Koch WJ, Rockman HA, Samama P, et al. Cardiac function in mice overexpressing the beta-adrenergic receptor kinase or a beta ARK inhibitor. Science. 1995;268:1350–1353
  25. Koch WJ, Lefkowitz RJ, Rockman HA, et al. Functional consequences of altering myocardial adrenergic receptor signaling. Annu Rev Physiol. 2000;62:237–260
  26. Krasel C, Dammeier S, Winstel R, et al. Phosphorylation of GRK2 by protein kinase C abolishes its inhibition by calmodulin. J Biol Chem. 2001;276:1911–1915
  27. Lefkowitz RJ, Shenoy SK. Transduction of receptor signals by beta-arrestins. Science. 2005;308:512–517
  28. Levay K, Satpaev DK, Pronin AN, et al. Localization of the sites for Ca2+-binding proteins on G protein-coupled receptor kinases. Biochemistry. 1998;37:13650–13659
  29. Liu S, Premont RT, Kontos CD, et al. A crucial role for GRK2 in regulation of endothelial cell nitric oxide synthase function in portal hypertension. Nat Med. 2005;11:952–958
  30. Lodowski DT, Pitcher JA, Capel WD, et al. Keeping G proteins at bay: a complex between G protein-coupled receptor kinase 2 and Gbetagamma. Science. 2003;300:1256–1262
  31. Lombardi MS, Kavelaars A, Penela P, et al. Oxidative stress decreases G protein-coupled receptor kinase 2 in lymphocytes via a calpain-dependent mechanism. Mol Pharmacol. 2002;62:379–388
  32. Lorenz K, Lohse MJ, Quitterer U. Protein kinase C switches the Raf kinase inhibitor from Raf-1 to GRK-2. Nature. 2003;426:574–579
  33. Loudon RP, Perussia B, Benovic JL. Differentially regulated expression of the G-protein-coupled receptor kinases, betaARK and GRK6, during myelomonocytic cell development in vitro. Blood. 1996;88:4547–4557
  34. Luo J, Benovic JL. G protein-coupled receptor kinase interaction with Hsp90 mediates kinase maturation. J Biol Chem. 2003;278:50908–50914
  35. Penela P, Alvarez-Dolado M, Munoz A, Mayor F. Expression patterns of the regulatory proteins G protein-coupled receptor kinase 2 and beta-arrestin 1 during rat postnatal brain development: effect of hypothyroidism. Eur J Biochem. 2000;267:4390–4396
  36. Penela P, Elorza A, Sarnago S, Mayor F. Beta-arrestin- and c-Src-dependent degradation of G-protein-coupled receptor kinase 2. EMBO J. 2001;20:5129–5138
  37. Penela P, Murga C, Ribas C, et al. Mechanisms of regulation of G protein-coupled receptor kinases (GRKs) and cardiovascular disease. Cardiovasc Res. 2006;69:46–56
  38. Ping P, Gelzer-Bell R, Roth DA, et al. Reduced beta-adrenergic receptor activation decreases G-protein expression and beta-adrenergic receptor kinase activity in porcine heart. J Clin Invest. 1995;95:1271–1280
  39. Pitcher JA, Inglese J, Higgins JB, et al. Role of beta gamma subunits of G proteins in targeting the beta-adrenergic receptor kinase to membrane-bound receptors. Science. 1992;257:1264–1267
  40. Pitcher JA, Freedman NJ, Lefkowitz RJ. G protein-coupled receptor kinases. Annu Rev Biochem. 1998;67:653–692
  41. Pitcher JA, Hall RA, Daaka Y, et al. The G protein-coupled receptor kinase 2 is a microtubule-associated protein kinase that phosphorylates tubulin. J Biol Chem. 1998;273:12316–12324
  42. Pitcher JA, Tesmer JJ, Freeman JL, et al. Feedback inhibition of G protein-coupled receptor kinase 2 (GRK2) activity by extracellular signal-regulated kinases. J Biol Chem. 1999;274:34531–34534
  43. Premont RT, Claing A, Vitale N, et al. beta2-Adrenergic receptor regulation by GIT1, a G protein-coupled receptor kinase-associated ADP ribosylation factor GTPase-activating protein. Proc Natl Acad Sci U S A. 1998;95:14082–14087
  44. Pronin AN, Morris AJ, Surguchov A, Benovic JL. Synucleins are a novel class of substrates for G protein-coupled receptor kinases. J Biol Chem. 2000;275:26515–26522
  45. Ramos-Ruiz R, Penela P, Penn RB, Mayor F. Analysis of the human G protein-coupled receptor kinase 2 (GRK2) gene promoter: regulation by signal transduction systems in aortic smooth muscle cells. Circulation. 2000;101:2083–2089
  46. Rockman HA, Choi DJ, Akhter SA, et al. Control of myocardial contractile function by the level of beta-adrenergic receptor kinase 1 in gene-targeted mice. J Biol Chem. 1998;273:18180–18184
  47. Rockman HA, Koch WJ, Lefkowitz RJ. Seven-transmembrane-spanning receptors and heart function. Nature. 2002;415:206–212
  48. Ruiz-Gomez A, Humrich J, Murga C, et al. Phosphorylation of phosducin and phosducin-like protein by G protein-coupled receptor kinase 2. J Biol Chem. 2000;275:29724–29730
  49. Rybin VO, Xu X, Lisanti MP, Steinberg SF, et al. Differential targeting of beta-adrenergic receptor subtypes and adenylyl cyclase to cardiomyocyte caveolae. A mechanism to functionally regulate the cAMP signaling pathway. J Biol Chem. 2000;275:41447–41457
  50. Sarnago S, Elorza A, Mayor F, et al. Agonist-dependent phosphorylation of the G protein-coupled receptor kinase 2 (GRK2) by Src tyrosine kinase. J Biol Chem. 1999;274:34411–34416
  51. Sarnago S, Roca R, de Blasi A, et al. Involvement of intramolecular interactions in the regulation of G protein-coupled receptor kinase 2. Mol Pharmacol. 2003;64:629–639
  52. Sefton M, Blanco MJ, Penela P, et al. Expression of the G protein-coupled receptor kinase 2 during early mouse embryogenesis. Mech Dev. 2000;98:127–131
  53. Shenoy SK, Lefkowitz RJ. Angiotensin II-stimulated signaling through G proteins and beta-arrestin. Sci STKE. 2005;cm14
  54. Sterne-Marr R, Tesmer JJ, Day PW, et al. G protein-coupled receptor Kinase 2/G alpha q/11 interaction. A novel surface on a regulator of G protein signaling homology domain for binding G alpha subunits. J Biol Chem. 2003;278:6050–6058
  55. Tesmer VM, Kawano T, Shankaranarayanan A, et al. Snapshot of activated G proteins at the membrane: the Galphaq-GRK2-Gbetagamma complex. Science. 2005;310:1686–1690
  56. Tevaearai HT, Koch WJ. Molecular restoration of beta-adrenergic receptor signaling improves contractile function of failing hearts. Trends Cardiovasc Med. 2004;14:252–256
  57. Theilade J, Lerche Hansen J, Haunso S, Sheikh SP. Extracellular signal-regulated kinases control expression of G protein-coupled receptor kinase 2 (GRK2). FEBS Lett. 2002;518:195–199
  58. Theilade J, Hansen JL, Haunso S, Sheikh SP. MAP kinase protects G protein-coupled receptor kinase 2 from proteasomal degradation. Biochem Biophys Res Commun. 2005;330:685–689
  59. Tohgo A, Pierce KL, Choy EW, et al. beta-Arrestin scaffolding of the ERK cascade enhances cytosolic ERK activity but inhibits ERK-mediated transcription following angiotensin AT1a receptor stimulation. J Biol Chem. 2002;277:9429–9436
  60. Touhara K. Binding of multiple ligands to pleckstrin homology domain regulates membrane translocation and enzyme activity of beta-adrenergic receptor kinase. FEBS Lett. 1997;417:243–248
  61. Ungerer M, Parruti G, Bohm M, et al. Expression of beta-arrestins and beta-adrenergic receptor kinases in the failing human heart. Circ Res. 1994;74:206–213
  62. Wan KF, Sambi BS, Tate R, et al. The inhibitory gamma subunit of the type 6 retinal cGMP phosphodiesterase functions to link c-Src and G-protein-coupled receptor kinase 2 in a signaling unit that regulates p42/p44 mitogen-activated protein kinase by epidermal growth factor. J Biol Chem. 2003;278:18658–18663
  63. Yu X, Huang S, Patterson E, et al. Proteasome degradation of GRK2 during ischemia and ventricular tachyarrhythmias in a canine model of myocardial infarction. Am J Physiol Heart Circ Physiol. 2005;289:H1960–H1967

PII: S1050-1738(06)00048-X

doi: 10.1016/j.tcm.2006.03.004

Trends in Cardiovascular Medicine
Volume 16, Issue 5 , Pages 169-177 , July 2006

Article Tools

* Image Usage & Resolution