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Gene Review

Adrbk2  -  adrenergic receptor kinase, beta 2

Mus musculus

Synonyms: 4833444A01Rik, AI851927, AW551196, Adrbk-2, Bark-2, ...
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Disease relevance of Adrbk2

  • CAMalpha(1B)AR-induced hypertrophy and ventricular atrial natriuretic factor expression were significantly attenuated with either concurrent GRK3 or GRK5 overexpression [1].
  • In addition, GRK3 -/- mice displayed an altered HR recovery from MCh-induced bradycardia [2].
  • Although direct stimulation of cardiac muscarinic receptors measured as vagal stimulation-induced bradycardia was similar in GRK3 -/- and wild-type mice, the baroreflex increase in HR associated with sodium nitroprusside-induced hypotension was significantly greater in GRK3 -/- than wild-type mice [2].

Psychiatry related information on Adrbk2

  • 2. Mice lacking GRK3 did not differ from wild-type littermates neither in their response latencies to noxious stimuli on the hot-plate test nor in their acute antinociceptive responses to fentanyl or morphine [3].

High impact information on Adrbk2

  • Therefore, we generated hybrid transgenic mice with myocardium-targeted overexpression of 1 of 3 GRKs expressed in the heart (GRK2 [commonly known as the beta-AR kinase 1], GRK3, or GRK5) with concomitant cardiac expression of a constitutively activated mutant (CAM) or wild-type alpha(1B)AR [1].
  • Transgenic mouse hearts overexpressing only GRK2, GRK3, or GRK5 had no hypertrophy [1].
  • In addition, activation of ERK1/2 by fentanyl and morphine was rescued in GRK3(-/-) neurons following transfection with dominant positive arrestin3-(R170E) [4].
  • Kappa opioid receptor activation of p38 MAPK is GRK3- and arrestin-dependent in neurons and astrocytes [5].
  • Another GRK3 mutant (GRK3-DeltaC), which lacked the C-terminal G(betagamma)-binding domain and which was not associated with oocyte membranes, also failed to induce GVBD [6].

Biological context of Adrbk2


Anatomical context of Adrbk2

  • The ability of beta ARK2 to phosphorylate various substrates was studied after expression in COS 7 cells [8].
  • We also demonstrated that three GRKs (GRK2, GRK3 and GRK5) are differentially distributed in the circumvallate papilla while only GRK2 is present in taste bud cells [10].
  • GRK3 -/- mice also displayed an enhanced sensitivity of the airway smooth muscle response to MCh [2].
  • 3. Tolerance to the electrophysiological response to the opioid fentanyl, measured in vitro in the hippocampus, was blocked by GRK3 deletion [3].

Associations of Adrbk2 with chemical compounds

  • In contrast, ERK1/2 activation by fentanyl was not evident in neurons from GRK3(-/-) mice or neurons pretreated with small inhibitory RNA for arrestin3 [4].
  • Overexpression of GRK3ct prevented not only the translocation of GRK3 and GRK2 but also the down-regulation of the alpha2B-AR caused by 24-h pretreatment with 20 microM EPI [9].
  • For all other antibodies, immunoreactivity was mostly restricted to the olfactory epithelial luminal border, confirming light microscopic studies that had shown that antibodies to GRK3, beta- arrestin-2, CaMKII, and PDE1C2 labeled this region [11].
  • In contrast, neither prodynorphin nor GRK3 knock-out mice showed U50,488 tolerance after pSNL [12].

Enzymatic interactions of Adrbk2

  • Although beta ARK2 is essentially equiactive with beta ARK in phosphorylating an acid-rich synthetic model peptide it was only approximately 50% as active when the substrate was the agonist-occupied beta 2-adrenergic receptor and only approximately 20% as active toward light-bleached rhodopsin [8].

Other interactions of Adrbk2

  • Two other genes, Adrbk2 at 60 cM and Nos1 at 65 cM, have biological plausibility in mechanisms of upper airway patency and chemosensitivity, respectively [13].
  • Direct sequencing of the PCR fragment provided a rapid means to identify the expression of the GRK2 but not the GRK3 transcript in these cells [7].
  • G protein-coupled receptor kinase 3 (GRK3) gene disruption leads to loss of odorant receptor desensitization [14].
  • This reduction in the ability to generate cAMP is evident even in the presence of nonodorant receptor stimuli (GTPgammaS and forskolin), suggesting a compensatory dampening of the G protein-adenylyl cyclase system in the GRK3 (-/-) mice in the olfactory epithelium [14].
  • Surprisingly, myocardial overexpression of GRK3 resulted in normal biochemical signaling through beta-adrenergic receptors (beta-ARs), and in vivo hemodynamic function in response to a beta-AR agonist was indistinguishable from that in nontransgenic controls [15].

Analytical, diagnostic and therapeutic context of Adrbk2

  • We found that these cells, which express GRK2, GRK3, GRK5, and GRK6 as well as beta-arrestins 1 and 2 as detected by RT-PCR and by Western blotting, were rapidly desensitized in the presence of FSH [16].


  1. Hybrid transgenic mice reveal in vivo specificity of G protein-coupled receptor kinases in the heart. Eckhart, A.D., Duncan, S.J., Penn, R.B., Benovic, J.L., Lefkowitz, R.J., Koch, W.J. Circ. Res. (2000) [Pubmed]
  2. Altered airway and cardiac responses in mice lacking G protein-coupled receptor kinase 3. Walker, J.K., Peppel, K., Lefkowitz, R.J., Caron, M.G., Fisher, J.T. Am. J. Physiol. (1999) [Pubmed]
  3. G-protein receptor kinase 3 (GRK3) influences opioid analgesic tolerance but not opioid withdrawal. Terman, G.W., Jin, W., Cheong, Y.P., Lowe, J., Caron, M.G., Lefkowitz, R.J., Chavkin, C. Br. J. Pharmacol. (2004) [Pubmed]
  4. Mu Opioid Receptor Activation of ERK1/2 Is GRK3 and Arrestin Dependent in Striatal Neurons. Macey, T.A., Lowe, J.D., Chavkin, C. J. Biol. Chem. (2006) [Pubmed]
  5. Kappa opioid receptor activation of p38 MAPK is GRK3- and arrestin-dependent in neurons and astrocytes. Bruchas, M.R., Macey, T.A., Lowe, J.D., Chavkin, C. J. Biol. Chem. (2006) [Pubmed]
  6. A G protein-coupled receptor kinase induces Xenopus oocyte maturation. Wang, J., Liu, X.J. J. Biol. Chem. (2003) [Pubmed]
  7. Cloning of GRK2 cDNA from S49 murine lymphoma cells. Hughes, R.J., Anderson, K.L., Kiel, D., Insel, P.A. Am. J. Physiol. (1996) [Pubmed]
  8. Cloning, expression, and chromosomal localization of beta-adrenergic receptor kinase 2. A new member of the receptor kinase family. Benovic, J.L., Onorato, J.J., Arriza, J.L., Stone, W.C., Lohse, M., Jenkins, N.A., Gilbert, D.J., Copeland, N.G., Caron, M.G., Lefkowitz, R.J. J. Biol. Chem. (1991) [Pubmed]
  9. 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]
  10. Characterization of bitter taste responses of intestinal STC-1 cells. Masuho, I., Tateyama, M., Saitoh, O. Chem. Senses (2005) [Pubmed]
  11. The fine-structural distribution of G-protein receptor kinase 3, beta-arrestin-2, Ca2+/calmodulin-dependent protein kinase II and phosphodiesterase PDE1C2, and a Cl(-)-cotransporter in rodent olfactory epithelia. Menco, B.P. J. Neurocytol. (2005) [Pubmed]
  12. Neuropathic pain activates the endogenous kappa opioid system in mouse spinal cord and induces opioid receptor tolerance. Xu, M., Petraschka, M., McLaughlin, J.P., Westenbroek, R.E., Caron, M.G., Lefkowitz, R.J., Czyzyk, T.A., Pintar, J.E., Terman, G.W., Chavkin, C. J. Neurosci. (2004) [Pubmed]
  13. Hypercapnic duty cycle is an intermediate physiological phenotype linked to mouse chromosome 5. Schneider, H., Patil, S.P., Canisius, S., Gladmon, E.A., Schwartz, A.R., O'Donnell, C.P., Smith, P.L., Tankersley, C.G. J. Appl. Physiol. (2003) [Pubmed]
  14. 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]
  15. Myocardial overexpression of GRK3 in transgenic mice: evidence for in vivo selectivity of GRKs. Iaccarino, G., Rockman, H.A., Shotwell, K.F., Tomhave, E.D., Koch, W.J. Am. J. Physiol. (1998) [Pubmed]
  16. Involvement of G protein-coupled receptor kinases and arrestins in desensitization to follicle-stimulating hormone action. Troispoux, C., Guillou, F., Elalouf, J.M., Firsov, D., Iacovelli, L., De Blasi, A., Combarnous, Y., Reiter, E. Mol. Endocrinol. (1999) [Pubmed]
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