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Gene Review

ADRBK1  -  adrenergic, beta, receptor kinase 1

Homo sapiens

Synonyms: BARK, BARK1, BETA-ARK1, Beta-ARK-1, Beta-adrenergic receptor kinase 1, ...
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Disease relevance of ADRBK1


Psychiatry related information on ADRBK1


High impact information on ADRBK1


Chemical compound and disease context of ADRBK1


Biological context of ADRBK1


Anatomical context of ADRBK1


Associations of ADRBK1 with chemical compounds


Physical interactions of ADRBK1

  • Cytosolic GRK activity in mononuclear cells decreased by 39 +/- 29%; cytosolic GRK2 and membrane-bound GRK6 decreased by 90 +/- 15 and 65 +/- 43%, respectively [27].
  • 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 regulator of the TGFbeta-signaling cascade [28].
  • Our data suggest that the D3R, filamin A, and beta-arrestin form a signaling complex that is destabilized by agonist- or expression-mediated increases in GRK2/3 activity [29].
  • In vitro binding assays show that the residues 498-502 of GRK2 bind the amino-terminal domain of clathrin heavy chain to almost the same extent as beta-arrestin1 [30].
  • However, these mGluR1a/Galphaq/11 interactions are not antagonized by the overexpression of either GRK2 mutants defective in Galphaq/11 binding or RGS4 [31].

Enzymatic interactions of ADRBK1


Co-localisations of ADRBK1

  • The beta(1)AR/GRK2 fusion protein internalizes via clathrin-coated pits and is found to co-localize with the endosome that contains transferrin [30].

Regulatory relationships of ADRBK1

  • The antibody-mediated inhibition was released by purified Gbetagamma subunits, strongly suggesting that Gbetagamma binding to the amino terminus of GRK2 enhances the kinase activity toward rhodopsin [16].
  • As assessed by ligand binding, the FSH-R was found expressed in the fractions where GRK 2 and beta-arrestins were recruited upon FSH treatment [37].
  • Coexpression of GRK2 strongly enhanced agonist-stimulated phosphorylation of the wild-type DOR (WT), but Delta15 or mutant DOR (T358A/T361A/S363G) failed to show any detectable phosphorylation under these conditions [38].
  • PDE4-selective inhibition also enhances the ability of isoprenaline to trigger the PKA phosphorylation of GRK2 in cardiac myocytes [39].
  • Here we show that AKAP79 also regulates the ability of GRK2 to phosphorylate agonist-occupied receptors [33].

Other interactions of ADRBK1


Analytical, diagnostic and therapeutic context of ADRBK1


  1. G protein-coupled receptor kinase 2 in multiple sclerosis and experimental autoimmune encephalomyelitis. Vroon, A., Kavelaars, A., Limmroth, V., Lombardi, M.S., Goebel, M.U., Van Dam, A.M., Caron, M.G., Schedlowski, M., Heijnen, C.J. J. Immunol. (2005) [Pubmed]
  2. Regulation of human melanocortin 1 receptor signaling and trafficking by thr-308 and ser-316 and its alteration in variant alleles associated with red hair and skin cancer. Sánchez-Laorden, B.L., Jiménez-Cervantes, C., García-Borrón, J.C. J. Biol. Chem. (2007) [Pubmed]
  3. Requirement of Gbetagamma and c-Src in D2 dopamine receptor-mediated nuclear factor-kappaB activation. Yang, M., Zhang, H., Voyno-Yasenetskaya, T., Ye, R.D. Mol. Pharmacol. (2003) [Pubmed]
  4. Neutrophil beta2-adrenergic receptor coupling efficiency to Gs protein in subjects with post-traumatic stress disorder and normal controls. Gurguis, G.N., Andrews, R., Antai-Otong, D., Vo, S.P., Blakeley, J.E., Orsulak, P.J., Rush, A.J. Psychopharmacology (Berl.) (1999) [Pubmed]
  5. Decreased immunodensities of micro-opioid receptors, receptor kinases GRK 2/6 and beta-arrestin-2 in postmortem brains of opiate addicts. Ferrer-Alcón, M., La Harpe, R., García-Sevilla, J.A. Brain Res. Mol. Brain Res. (2004) [Pubmed]
  6. Lymphocyte G-protein-coupled receptor kinase-2 is upregulated in patients with Alzheimer's disease. Leosco, D., Fortunato, F., Rengo, G., Iaccarino, G., Sanzari, E., Golino, L., Zincarelli, C., Canonico, V., Marchese, M., Koch, W.J., Rengo, F. Neurosci. Lett. (2007) [Pubmed]
  7. Isoprenylation in regulation of signal transduction by G-protein-coupled receptor kinases. Inglese, J., Koch, W.J., Caron, M.G., Lefkowitz, R.J. Nature (1992) [Pubmed]
  8. Removal of phosphorylation sites from the beta 2-adrenergic receptor delays onset of agonist-promoted desensitization. Bouvier, M., Hausdorff, W.P., De Blasi, A., O'Dowd, B.F., Kobilka, B.K., Caron, M.G., Lefkowitz, R.J. Nature (1988) [Pubmed]
  9. Molecular basis for interactions of G protein betagamma subunits with effectors. Ford, C.E., Skiba, N.P., Bae, H., Daaka, Y., Reuveny, E., Shekter, L.R., Rosal, R., Weng, G., Yang, C.S., Iyengar, R., Miller, R.J., Jan, L.Y., Lefkowitz, R.J., Hamm, H.E. Science (1998) [Pubmed]
  10. Role of beta-arrestin in mediating agonist-promoted G protein-coupled receptor internalization. Ferguson, S.S., Downey, W.E., Colapietro, A.M., Barak, L.S., Ménard, L., Caron, M.G. Science (1996) [Pubmed]
  11. Inhibition of constitutive signaling of Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor by protein kinases in mammalian cells in culture. Geras-Raaka, E., Arvanitakis, L., Bais, C., Cesarman, E., Mesri, E.A., Gershengorn, M.C. J. Exp. Med. (1998) [Pubmed]
  12. The full-length, cytoplasmic C-terminus of the beta 2-adrenergic receptor expressed in E. coli acts as a substrate for phosphorylation by protein kinase A, insulin receptor tyrosine kinase, GRK2, but not protein kinase C and suppresses desensitization when expressed in vivo. Doronin, S., Lin, F., Wang, H.Y., Malbon, C.C. Protein Expr. Purif. (2000) [Pubmed]
  13. Hydrogen peroxide impairs GRK2 translation via a calpain-dependent and cdk1-mediated pathway. Cobelens, P.M., Kavelaars, A., Heijnen, C.J., Ribas, C., Mayor, F., Penela, P. Cell. Signal. (2007) [Pubmed]
  14. Cardiac-specific ablation of G-protein receptor kinase 2 redefines its roles in heart development and beta-adrenergic signaling. Matkovich, S.J., Diwan, A., Klanke, J.L., Hammer, D.J., Marreez, Y., Odley, A.M., Brunskill, E.W., Koch, W.J., Schwartz, R.J., Dorn, G.W. Circ. Res. (2006) [Pubmed]
  15. Beta-arrestin- and c-Src-dependent degradation of G-protein-coupled receptor kinase 2. Penela, P., Elorza, A., Sarnago, S., Mayor, F. EMBO J. (2001) [Pubmed]
  16. The amino-terminal domain of G-protein-coupled receptor kinase 2 is a regulatory Gbeta gamma binding site. Eichmann, T., Lorenz, K., Hoffmann, M., Brockmann, J., Krasel, C., Lohse, M.J., Quitterer, U. J. Biol. Chem. (2003) [Pubmed]
  17. Inhibition of G protein-coupled receptor kinase subtypes by Ca2+/calmodulin. Chuang, T.T., Paolucci, L., De Blasi, A. J. Biol. Chem. (1996) [Pubmed]
  18. Role of G protein-coupled receptor kinases in glucose-dependent insulinotropic polypeptide receptor signaling. Tseng, C.C., Zhang, X.Y. Endocrinology (2000) [Pubmed]
  19. Assignment of the beta-arrestin 1 gene (ARRB1) to human chromosome 11q13. Calabrese, G., Sallese, M., Stornaiuolo, A., Morizio, E., Palka, G., De Blasi, A. Genomics (1994) [Pubmed]
  20. Regulation of G protein-coupled receptor kinase subtypes in activated T lymphocytes. Selective increase of beta-adrenergic receptor kinase 1 and 2. De Blasi, A., Parruti, G., Sallese, M. J. Clin. Invest. (1995) [Pubmed]
  21. Monocyte chemoattractant protein-1-induced CCR2B receptor desensitization mediated by the G protein-coupled receptor kinase 2. Aragay, A.M., Mellado, M., Frade, J.M., Martin, A.M., Jimenez-Sainz, M.C., Martinez-A, C., Mayor, F. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  22. Monoclonal antibodies reveal receptor specificity among G-protein-coupled receptor kinases. Oppermann, M., Diversé-Pierluissi, M., Drazner, M.H., Dyer, S.L., Freedman, N.J., Peppel, K.C., Lefkowitz, R.J. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  23. G protein-coupled receptor kinase interaction with Hsp90 mediates kinase maturation. Luo, J., Benovic, J.L. J. Biol. Chem. (2003) [Pubmed]
  24. G protein-coupled receptor kinase 2-mediated phosphorylation of ezrin is required for G protein-coupled receptor-dependent reorganization of the actin cytoskeleton. Cant, S.H., Pitcher, J.A. Mol. Biol. Cell (2005) [Pubmed]
  25. Bimodal regulation of the human H1 histamine receptor by G protein-coupled receptor kinase 2. Iwata, K., Luo, J., Penn, R.B., Benovic, J.L. J. Biol. Chem. (2005) [Pubmed]
  26. Effect of different G protein-coupled receptor kinases on phosphorylation and desensitization of the alpha1B-adrenergic receptor. Diviani, D., Lattion, A.L., Larbi, N., Kunapuli, P., Pronin, A., Benovic, J.L., Cotecchia, S. J. Biol. Chem. (1996) [Pubmed]
  27. Cardiopulmonary bypass decreases G protein-coupled receptor kinase activity and expression in human peripheral blood mononuclear cells. Hagen, S.A., Kondyra, A.L., Grocott, H.P., El-Moalem, H., Bainbridge, D., Mathew, J.P., Newman, M.F., Reves, J.G., Schwinn, D.A., Kwatra, M.M. Anesthesiology (2003) [Pubmed]
  28. The G protein-coupled receptor kinase-2 is a TGFbeta-inducible antagonist of TGFbeta signal transduction. Ho, J., Cocolakis, E., Dumas, V.M., Posner, B.I., Laporte, S.A., Lebrun, J.J. EMBO J. (2005) [Pubmed]
  29. G protein-coupled receptor kinase regulates dopamine D3 receptor signaling by modulating the stability of a receptor-filamin-beta-arrestin complex. A case of autoreceptor regulation. Kim, K.M., Gainetdinov, R.R., Laporte, S.A., Caron, M.G., Barak, L.S. J. Biol. Chem. (2005) [Pubmed]
  30. Clathrin box in G protein-coupled receptor kinase 2. Shiina, T., Arai, K., Tanabe, S., Yoshida, N., Haga, T., Nagao, T., Kurose, H. J. Biol. Chem. (2001) [Pubmed]
  31. G Protein-coupled receptor kinase 2 regulator of G protein signaling homology domain binds to both metabotropic glutamate receptor 1a and Galphaq to attenuate signaling. Dhami, G.K., Dale, L.B., Anborgh, P.H., O'Connor-Halligan, K.E., Sterne-Marr, R., Ferguson, S.S. J. Biol. Chem. (2004) [Pubmed]
  32. The beta-adrenergic receptor kinase (GRK2) is regulated by phospholipids. Onorato, J.J., Gillis, M.E., Liu, Y., Benovic, J.L., Ruoho, A.E. J. Biol. Chem. (1995) [Pubmed]
  33. Regulation of membrane targeting of the G protein-coupled receptor kinase 2 by protein kinase A and its anchoring protein AKAP79. Cong, M., Perry, S.J., Lin, F.T., Fraser, I.D., Hu, L.A., Chen, W., Pitcher, J.A., Scott, J.D., Lefkowitz, R.J. J. Biol. Chem. (2001) [Pubmed]
  34. Feedback inhibition of G protein-coupled receptor kinase 2 (GRK2) activity by extracellular signal-regulated kinases. Pitcher, J.A., Tesmer, J.J., Freeman, J.L., Capel, W.D., Stone, W.C., Lefkowitz, R.J. J. Biol. Chem. (1999) [Pubmed]
  35. Agonist-dependent phosphorylation of the G protein-coupled receptor kinase 2 (GRK2) by Src tyrosine kinase. Sarnago, S., Elorza, A., Mayor, F. J. Biol. Chem. (1999) [Pubmed]
  36. Identification of phosphorylation sites in the G protein-coupled receptor for parathyroid hormone. Receptor phosphorylation is not required for agonist-induced internalization. Malecz, N., Bambino, T., Bencsik, M., Nissenson, R.A. Mol. Endocrinol. (1998) [Pubmed]
  37. G protein-coupled receptor kinase 2 and beta-arrestins are recruited to FSH receptor in stimulated rat primary Sertoli cells. Marion, S., Kara, E., Crepieux, P., Piketty, V., Martinat, N., Guillou, F., Reiter, E. J. Endocrinol. (2006) [Pubmed]
  38. Identification of G protein-coupled receptor kinase 2 phosphorylation sites responsible for agonist-stimulated delta-opioid receptor phosphorylation. Guo, J., Wu, Y., Zhang, W., Zhao, J., Devi, L.A., Pei, G., Ma, L. Mol. Pharmacol. (2000) [Pubmed]
  39. Phosphodiesterase-4 influences the PKA phosphorylation status and membrane translocation of G-protein receptor kinase 2 (GRK2) in HEK-293beta2 cells and cardiac myocytes. Li, X., Huston, E., Lynch, M.J., Houslay, M.D., Baillie, G.S. Biochem. J. (2006) [Pubmed]
  40. An approach to the study of G-protein-coupled receptor kinases: an in vitro-purified membrane assay reveals differential receptor specificity and regulation by G beta gamma subunits. Pei, G., Tiberi, M., Caron, M.G., Lefkowitz, R.J. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  41. Phosphorylation and desensitization of the human beta 1-adrenergic receptor. Involvement of G protein-coupled receptor kinases and cAMP-dependent protein kinase. Freedman, N.J., Liggett, S.B., Drachman, D.E., Pei, G., Caron, M.G., Lefkowitz, R.J. J. Biol. Chem. (1995) [Pubmed]
  42. Phosphorylation of phosducin and phosducin-like protein by G protein-coupled receptor kinase 2. Ruiz-Gómez, A., Humrich, J., Murga, C., Quitterer, U., Lohse, M.J., Mayor, F. J. Biol. Chem. (2000) [Pubmed]
  43. Mdm2 is involved in the ubiquitination and degradation of G-protein-coupled receptor kinase 2. Salcedo, A., Mayor, F., Penela, P. EMBO J. (2006) [Pubmed]
  44. Beta 2-adrenergic receptor stimulated, G protein-coupled receptor kinase 2 mediated, phosphorylation of ribosomal protein P2. Freeman, J.L., Gonzalo, P., Pitcher, J.A., Claing, A., Lavergne, J.P., Reboud, J.P., Lefkowitz, R.J. Biochemistry (2002) [Pubmed]
  45. Characterization of the GRK2 binding site of Galphaq. Day, P.W., Tesmer, J.J., Sterne-Marr, R., Freeman, L.C., Benovic, J.L., Wedegaertner, P.B. J. Biol. Chem. (2004) [Pubmed]
  46. Phosphorylation of GRK2 by protein kinase C abolishes its inhibition by calmodulin. Krasel, C., Dammeier, S., Winstel, R., Brockmann, J., Mischak, H., Lohse, M.J. J. Biol. Chem. (2001) [Pubmed]
  47. Decreased expression of G protein-coupled receptor kinases in the detrusor smooth muscle of human urinary bladder with outlet obstruction. Furuya, Y., Araki, I., Kamiyama, M., Zakoji, H., Takihana, Y., Takeda, M. International journal of urology : official journal of the Japanese Urological Association. (2006) [Pubmed]
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