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Gene Review

GRK4  -  G protein-coupled receptor kinase 4

Homo sapiens

Synonyms: G protein-coupled receptor kinase GRK4, GPRK2L, GPRK4, GRK4a, IT11, ...
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Disease relevance of GRK4


High impact information on GRK4

  • Surprisingly, this desensitization occurred in the absence of ligand-induced receptor phosphorylation and could be promoted by GRK4 mutants deleted of their kinase domain [3].
  • Reciprocally, transfection of GRK4 in HEK293 cells restored agonist-promoted desensitization, confirming that this kinase is sufficient to support desensitization [3].
  • Taking advantage of this cell-specific desensitization phenotype, we identified GRK4 as the kinase involved in the neuronal desensitization [3].
  • G protein-coupled receptor kinase 4 gene variants in human essential hypertension [4].
  • These results suggest that the GRK4 subfamily of GRKs may play a signaling role in the nucleus and that GRK4 and GRK2 subfamily members perform divergent cellular functions [5].

Biological context of GRK4


Anatomical context of GRK4


Associations of GRK4 with chemical compounds


Other interactions of GRK4

  • Interestingly, similar regions in GRK4 and GRK6 appear to be palmitoylated (and involved in membrane interaction), suggesting evolutionary conservation of the function of this domain [17].
  • The genomic organization of the GRK4 gene is completely distinct from that of the human GRK2 gene, highlighting the evolutionary distance since the divergence of these two genes [6].
  • Antibodies to GRK2, GRK3 and GRK4 were used to confirm the presence of the protein product in the human urinary bladder using immunohistochemical staining and the western blotting technique [18].
  • Using PCR we found that G protein-coupled receptor kinase4 (GRK4) mRNA is expressed only in brain out of several tissues tested [19].
  • Phosphatidylinositol-binding sequences more distantly related to HIKE are present in gelsolin, in the G protein-coupled receptor kinase 4 and in Trop-2 [20].

Analytical, diagnostic and therapeutic context of GRK4


  1. Association of G-protein-coupled receptor kinase 4 haplotypes, but not HSD3B1 or PTP1B polymorphisms, with essential hypertension. Speirs, H.J., Katyk, K., Kumar, N.N., Benjafield, A.V., Wang, W.Y., Morris, B.J. J. Hypertens. (2004) [Pubmed]
  2. Homology of the 70-kilodalton antigens from Mycobacterium leprae and Mycobacterium bovis with the Mycobacterium tuberculosis 71-kilodalton antigen and with the conserved heat shock protein 70 of eucaryotes. Garsia, R.J., Hellqvist, L., Booth, R.J., Radford, A.J., Britton, W.J., Astbury, L., Trent, R.J., Basten, A. Infect. Immun. (1989) [Pubmed]
  3. Phosphorylation-independent desensitization of GABA(B) receptor by GRK4. Perroy, J., Adam, L., Qanbar, R., Chénier, S., Bouvier, M. EMBO J. (2003) [Pubmed]
  4. G protein-coupled receptor kinase 4 gene variants in human essential hypertension. Felder, R.A., Sanada, H., Xu, J., Yu, P.Y., Wang, Z., Watanabe, H., Asico, L.D., Wang, W., Zheng, S., Yamaguchi, I., Williams, S.M., Gainer, J., Brown, N.J., Hazen-Martin, D., Wong, L.J., Robillard, J.E., Carey, R.M., Eisner, G.M., Jose, P.A. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  5. G protein-coupled receptor kinase 5 contains a DNA-binding nuclear localization sequence. Johnson, L.R., Scott, M.G., Pitcher, J.A. Mol. Cell. Biol. (2004) [Pubmed]
  6. Characterization of the G protein-coupled receptor kinase GRK4. Identification of four splice variants. Premont, R.T., Macrae, A.D., Stoffel, R.H., Chung, N., Pitcher, J.A., Ambrose, C., Inglese, J., MacDonald, M.E., Lefkowitz, R.J. J. Biol. Chem. (1996) [Pubmed]
  7. Regulation of G protein-coupled receptor kinases by calmodulin and localization of the calmodulin binding domain. Pronin, A.N., Satpaev, D.K., Slepak, V.Z., Benovic, J.L. J. Biol. Chem. (1997) [Pubmed]
  8. G protein-coupled receptor kinase GRK4. Molecular analysis of the four isoforms and ultrastructural localization in spermatozoa and germinal cells. Sallese, M., Mariggiò, S., Collodel, G., Moretti, E., Piomboni, P., Baccetti, B., De Blasi, A. J. Biol. Chem. (1997) [Pubmed]
  9. The GRK4 subfamily of G protein-coupled receptor kinases. Alternative splicing, gene organization, and sequence conservation. Premont, R.T., Macrae, A.D., Aparicio, S.A., Kendall, H.E., Welch, J.E., Lefkowitz, R.J. J. Biol. Chem. (1999) [Pubmed]
  10. Novel features of G protein-coupled receptor kinase 4. Neve, K.A. Mol. Pharmacol. (2006) [Pubmed]
  11. Role of G protein-coupled receptor kinase 4 and beta-arrestin 1 in agonist-stimulated metabotropic glutamate receptor 1 internalization and activation of mitogen-activated protein kinases. Iacovelli, L., Salvatore, L., Capobianco, L., Picascia, A., Barletta, E., Storto, M., Mariggiò, S., Sallese, M., Porcellini, A., Nicoletti, F., De Blasi, A. J. Biol. Chem. (2003) [Pubmed]
  12. Role of G protein-coupled receptor kinases on the agonist-induced phosphorylation and internalization of the follitropin receptor. Lazari, M.F., Liu, X., Nakamura, K., Benovic, J.L., Ascoli, M. Mol. Endocrinol. (1999) [Pubmed]
  13. Single-nucleotide polymorphisms for diagnosis of salt-sensitive hypertension. Sanada, H., Yatabe, J., Midorikawa, S., Hashimoto, S., Watanabe, T., Moore, J.H., Ritchie, M.D., Williams, S.M., Pezzullo, J.C., Sasaki, M., Eisner, G.M., Jose, P.A., Felder, R.A. Clin. Chem. (2006) [Pubmed]
  14. Dopamine and the kidney: a role in hypertension? Jose, P.A., Eisner, G.M., Felder, R.A. Curr. Opin. Nephrol. Hypertens. (2003) [Pubmed]
  15. The D1 dopamine receptor is constitutively phosphorylated by G protein-coupled receptor kinase 4. Rankin, M.L., Marinec, P.S., Cabrera, D.M., Wang, Z., Jose, P.A., Sibley, D.R. Mol. Pharmacol. (2006) [Pubmed]
  16. G protein-coupled receptor kinase 4 (GRK4) regulates the phosphorylation and function of the dopamine D3 receptor. Villar, V.A., Jones, J.E., Armando, I., Palmes-Saloma, C., Yu, P., Pascua, A.M., Keever, L., Arnaldo, F.B., Wang, Z., Luo, Y., Felder, R.A., Jose, P.A. J. Biol. Chem. (2009) [Pubmed]
  17. Structure-function analysis of G protein-coupled receptor kinase-5. Role of the carboxyl terminus in kinase regulation. Pronin, A.N., Carman, C.V., Benovic, J.L. J. Biol. Chem. (1998) [Pubmed]
  18. 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]
  19. Two isoforms of G protein-coupled receptor kinase 4 identified by molecular cloning. Sallese, M., Lombardi, M.S., De Blasi, A. Biochem. Biophys. Res. Commun. (1994) [Pubmed]
  20. Large and diverse numbers of human diseases with HIKE mutations. Ciccarelli, F.D., Acciarito, A., Alberti, S. Hum. Mol. Genet. (2000) [Pubmed]
  21. Association study of g protein-coupled receptor kinase 4 gene variants with essential hypertension in northern han chinese. Wang, Y., Li, B., Zhao, W., Liu, P., Zhao, Q., Chen, S., Li, H., Gu, D. Ann. Hum. Genet. (2006) [Pubmed]
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