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Gene Review

Grk1  -  G protein-coupled receptor kinase 1

Mus musculus

Synonyms: Gprk1, RK, Rhodopsin kinase, Rhok, Rk
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Disease relevance of Grk1

  • LPA-induced PKD activation was modestly attenuated by prior exposure of RK cells to pertussis toxin (PTx) but abolished by the combination treatments of PTx and Clostridium difficile toxin B [1].
  • The major and consistent finding in transgenic APP/RK mice that died prematurely was extensive neurodegeneration and apoptosis, mainly in hippocampus and cortex, and accompanied by astrocytosis throughout the brain [2].

High impact information on Grk1

  • Other ubiquitously expressed ARFGAPs, G protein-coupled receptor kinase interactors GIT2 and GIT2-short/KIAA0148, which we have shown to exhibit GAP activity for ARF1 in COS-7 cells, did not accumulate at the phagocytic cups or inhibit phagocytosis [3].
  • Outer segment membranes of GC1(-/-) and GC double knock-out cones were destabilized and devoid of cone transducin (alpha- and gamma-subunits), cone phosphodiesterase, and G protein-coupled receptor kinase 1, whereas cone pigments were present at reduced levels [4].
  • G protein-coupled receptor kinase 3 (GRK3) gene disruption leads to loss of odorant receptor desensitization [5].
  • The role of the G-protein receptor kinase Grk1 in cone pigment inactivation was investigated in recordings from Nrl-/-/Grk1-/- photoreceptors [6].
  • Thus, Grk1 is essential to normal inactivation of both S- and M-mouse cone opsins, but S-opsin has access to a relatively effective, Grk1-independent inactivation pathway [6].

Biological context of Grk1


Anatomical context of Grk1

  • In contrast, cArr did not stably associate with light-adapted membranes in either wild-type or Grk1-/- retinas under our experimental conditions, but redistributed to the cone outer segments in a light-dependent manner [10].
  • Neither amyloid deposits nor neurofibrillary tangles were detected in the brain of APP/RK transgenic mice, even when 15-months-old [2].

Associations of Grk1 with chemical compounds

  • In contrast, the regulatory subunit-cyclic AMP complex from R kinase is stable to heat inactivation only when formed in the presence of high cyclic AMP concentrations (10(-5)M) [9].

Other interactions of Grk1


Analytical, diagnostic and therapeutic context of Grk1

  • Immunoblotting revealed that approximately 25-50% of Arr associated with the membrane in light-adapted wild-type, Grk1-/- and Gnat1-/-/Grk1-/- mouse retinas [10].


  1. Cooperation of Gq, Gi, and G12/13 in protein kinase D activation and phosphorylation induced by lysophosphatidic acid. Yuan, J., Slice, L.W., Gu, J., Rozengurt, E. J. Biol. Chem. (2003) [Pubmed]
  2. Premature death in transgenic mice that overexpress a mutant amyloid precursor protein is preceded by severe neurodegeneration and apoptosis. Moechars, D., Lorent, K., Van Leuven, F. Neuroscience (1999) [Pubmed]
  3. PAG3/Papalpha/KIAA0400, a GTPase-activating protein for ADP-ribosylation factor (ARF), regulates ARF6 in Fcgamma receptor-mediated phagocytosis of macrophages. Uchida, H., Kondo, A., Yoshimura, Y., Mazaki, Y., Sabe, H. J. Exp. Med. (2001) [Pubmed]
  4. The function of guanylate cyclase 1 and guanylate cyclase 2 in rod and cone photoreceptors. Baehr, W., Karan, S., Maeda, T., Luo, D.G., Li, S., Bronson, J.D., Watt, C.B., Yau, K.W., Frederick, J.M., Palczewski, K. J. Biol. Chem. (2007) [Pubmed]
  5. G protein-coupled receptor kinase 3 (GRK3) gene disruption leads to loss of odorant receptor desensitization. Peppel, K., Boekhoff, I., McDonald, P., Breer, H., Caron, M.G., Lefkowitz, R.J. J. Biol. Chem. (1997) [Pubmed]
  6. Photoreceptors of Nrl -/- mice coexpress functional S- and M-cone opsins having distinct inactivation mechanisms. Nikonov, S.S., Daniele, L.L., Zhu, X., Craft, C.M., Swaroop, A., Pugh, E.N. J. Gen. Physiol. (2005) [Pubmed]
  7. Involvement of G protein-coupled receptor kinase (GRK) 3 and GRK2 in down-regulation of the alpha2B-adrenoceptor. Desai, A.N., Salim, S., Standifer, K.M., Eikenburg, D.C. J. Pharmacol. Exp. Ther. (2006) [Pubmed]
  8. GRK6 deficiency is associated with enhanced CXCR4-mediated neutrophil chemotaxis in vitro and impaired responsiveness to G-CSF in vivo. Vroon, A., Heijnen, C.J., Raatgever, R., Touw, I.P., Ploemacher, R.E., Premont, R.T., Kavelaars, A. J. Leukoc. Biol. (2004) [Pubmed]
  9. Altered regulation of cyclic AMP-dependent protein kinase in a mouse lymphoma cell line. Lasser, M., Daniel, V. Biochim. Biophys. Acta (1977) [Pubmed]
  10. Light-dependent redistribution of visual arrestins and transducin subunits in mice with defective phototransduction. Zhang, H., Huang, W., Zhang, H., Zhu, X., Craft, C.M., Baehr, W., Chen, C.K. Mol. Vis. (2003) [Pubmed]
  11. Agonist activated adrenocorticotropin receptor internalizes via a clathrin-mediated G protein receptor kinase dependent mechanism. Baig, A.H., Swords, F.M., Szaszák, M., King, P.J., Hunyady, L., Clark, A.J. Endocr. Res. (2002) [Pubmed]
  12. G protein-coupled receptor kinase/beta-arrestin systems and drugs of abuse: psychostimulant and opiate studies in knockout mice. Bohn, L.M., Gainetdinov, R.R., Caron, M.G. Neuromolecular Med. (2004) [Pubmed]
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