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Gene Review

Gnb2l1  -  guanine nucleotide binding protein (G...

Rattus norvegicus

Synonyms: Guanine nucleotide-binding protein subunit beta-2-like 1, RACK1, Receptor for activated C kinase, Receptor of activated protein kinase C 1
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Disease relevance of Gnb2l1

  • The receptor for activated C kinase (RACK1) mRNA expression in kidneys obtained from rats 12 h following ischemia is enhanced twofold compared with sham-operated rats [1].

Psychiatry related information on Gnb2l1

  • Since RACK1 facilitates the PKC substrate accessibility, driving its cellular localization, the coordinate regulation of the PKC/RACK system by morphine could be a relevant molecular mechanism in opiate addiction [2].

High impact information on Gnb2l1

  • RACK1 binds to inositol 1,4,5-trisphosphate receptors and mediates Ca2+ release [3].
  • Overexpression of RACK1 or depletion of RACK1 by interference RNA markedly augments or diminishes Ca2+ release, respectively, without affecting Ca2+ entry [3].
  • We further found that in hippocampal slices, both RACK1 and NR2B associated with another WD40 protein, the beta-subunit of G protein (Gbeta), previously shown to heterodimerize with RACK1 in vitro (Dell, E. J., Connor, J., Chen, S., Stebbins, E. G., Skiba, N. P., Mochly-Rosen, D., and Hamm, H. E. (2002) J. Biol. Chem. 277, 49888-49895) [4].
  • We therefore tested the hypothesis that RACK1 forms a homodimer that allows the simultaneous binding of Fyn and NR2B [4].
  • Spatial and temporal regulation of RACK1 function and N-methyl-D-aspartate receptor activity through WD40 motif-mediated dimerization [4].

Biological context of Gnb2l1

  • During acute exposure to ethanol, RACK1 is dissociated from the complex, thereby facilitating Fyn-mediated phosphorylation of NR2B, which enhances channel activity, counteracting the inhibitory actions of ethanol [5].
  • Use of RACK1 antisense oligonucleotide reduced the ability of young macrophages to respond to LPS, further supporting the idea that a deficit in RACK1 contributes to the functional impairment in aged macrophages and that age-induced macrophage immunodeficiencies are associated with alteration in signal transduction pathways [6].
  • The mouse RACK1 gene is regulated by nuclear factor-kappa B and contributes to cell survival [7].
  • We found that nuclear RACK1 is mediating the induction of the immediate early gene c-fos expression induced by ethanol [8].
  • To better understand its function, we cloned the mouse RACK1 gene and found it contains eight exons and seven introns, and maps to mouse chromosome 11B1.2-1 [7].

Anatomical context of Gnb2l1

  • These results indicate that in astrocytes, RACK1 and PKC-betaII synchronous relocation is not essential for relocation of PKC-betaII to the PM [9].
  • Because RACK1 and PKC-betaII relocation seemed not to be synchronous, we hypothesized that an intermediate interaction with the cytoskeleton was taking place [9].
  • In this study, age-associated changes in the release of TNF-alpha from LPS-stimulated rat alveolar macrophages were determined and correlated with a decrease in the level of RACK1, the anchoring protein involved in protein kinase C translocation and activation [6].
  • Proteins homologous to all but one rat 40S subunit protein, including a homolog of RACK1, and all but three rat 60S subunit proteins were identified as components of the C. reinhardtii ribosome [10].
  • Recently, we found that in cultured cells and in vivo, acute ethanol exposure induces the nuclear compartmentalization of RACK1 [8].

Associations of Gnb2l1 with chemical compounds

  • We previously found that at least part of the RACK1-binding site resides in the C2 domain of betaIIPKC (Ron, D., Luo, J., and Mochly-Rosen, D. (1995) J. Biol. Chem. 270, 24180-24187) [11].
  • Here we show that following stimulation with glucose, alphaPKC and epsilonPKC translocate to the cell's periphery, while deltaPKC and zetaPKC translocate to perinuclear sites. betaC2-4, a peptide derived from the RACK1-binding site in the C2 domain of betaPKC, inhibits translocation of alphaPKC and reduces insulin response to glucose [12].
  • We first found that a C2-containing fragment, but not a C1-containing fragment of beta PKC, bound to RACK1 and inhibited subsequent beta PKC binding [13].
  • Pre-treatment with 1 nmbeta-estradiol, which reduced by approximately 35% the expression of RACK-1, prevented the lipopolysaccharide-induced expression of tumour necrosis factor-alpha mRNA and of the inducible form of nitric oxide (NO) synthase [14].
  • These results demonstrate that estrogen reduction of the RACK-1 expression, leading to a defective protein kinase-C activation counteracts the inflammatory response in astrocytes [14].

Regulatory relationships of Gnb2l1

  • However, transduction of exogenous RACK1 expressed as a Tat-fusion protein was able to rescue c-fos mRNA expression after chronic ethanol exposure [15].

Other interactions of Gnb2l1

  • 2. Acute morphine (30 mg kg(-1), i.p., 2 h) induced significant increases in the densities of RACK1 (33%), PKC-alpha (35%) and PKC-beta (23%) [2].
  • These results indicate that a deficit in RACK1 may contribute to the functional impairment in PKC activation observed in aged rat brain [16].
  • RACK1 translocates to the nucleus after exposure of neurons to ethanol and increases expression of BDNF (McGough et al., 2004) [17].
  • First, transduction of full-length RACK1 (Tat-RACK1) resulted in the induction of c-fos expression and enhancement of ethanol activities [8].
  • We characterised the ontogenesis of PKC betaII and its anchoring protein RACK1 in correlation with PKC-dependent immune functions, such as TNF-alpha, hydrogen peroxide production and lysozyme release in resident alveolar macrophages obtained from rats 2, 4 and 12 weeks old [18].

Analytical, diagnostic and therapeutic context of Gnb2l1


  1. Ischemia-induced receptor for activated C kinase (RACK1) expression in rat kidneys. Padanilam, B.J., Hammerman, M.R. Am. J. Physiol. (1997) [Pubmed]
  2. Parallel modulation of receptor for activated C kinase 1 and protein kinase C-alpha and beta isoforms in brains of morphine-treated rats. Escribá, P.V., García-Sevilla, J.A. Br. J. Pharmacol. (1999) [Pubmed]
  3. RACK1 binds to inositol 1,4,5-trisphosphate receptors and mediates Ca2+ release. Patterson, R.L., van Rossum, D.B., Barrow, R.K., Snyder, S.H. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  4. Spatial and temporal regulation of RACK1 function and N-methyl-D-aspartate receptor activity through WD40 motif-mediated dimerization. Thornton, C., Tang, K.C., Phamluong, K., Luong, K., Vagts, A., Nikanjam, D., Yaka, R., Ron, D. J. Biol. Chem. (2004) [Pubmed]
  5. Scaffolding of Fyn kinase to the NMDA receptor determines brain region sensitivity to ethanol. Yaka, R., Phamluong, K., Ron, D. J. Neurosci. (2003) [Pubmed]
  6. A defective protein kinase C anchoring system underlying age-associated impairment in TNF-alpha production in rat macrophages. Corsini, E., Battaini, F., Lucchi, L., Marinovich, M., Racchi, M., Govoni, S., Galli, C.L. J. Immunol. (1999) [Pubmed]
  7. The mouse RACK1 gene is regulated by nuclear factor-kappa B and contributes to cell survival. Choi, D.S., Young, H., McMahon, T., Wang, D., Messing, R.O. Mol. Pharmacol. (2003) [Pubmed]
  8. Ethanol induces gene expression via nuclear compartmentalization of receptor for activated C kinase 1. He, D.Y., Vagts, A.J., Yaka, R., Ron, D. Mol. Pharmacol. (2002) [Pubmed]
  9. Translocation of protein kinase C-betaII in astrocytes requires organized actin cytoskeleton and is not accompanied by synchronous RACK1 relocation. Pascale, A., Alkon, D.L., Grimaldi, M. Glia (2004) [Pubmed]
  10. Composition and structure of the 80S ribosome from the green alga Chlamydomonas reinhardtii: 80S ribosomes are conserved in plants and animals. Manuell, A.L., Yamaguchi, K., Haynes, P.A., Milligan, R.A., Mayfield, S.P. J. Mol. Biol. (2005) [Pubmed]
  11. Binding specificity for RACK1 resides in the V5 region of beta II protein kinase C. Stebbins, E.G., Mochly-Rosen, D. J. Biol. Chem. (2001) [Pubmed]
  12. Translocation inhibitors define specificity of protein kinase C isoenzymes in pancreatic beta-cells. Yedovitzky, M., Mochly-Rosen, D., Johnson, J.A., Gray, M.O., Ron, D., Abramovitch, E., Cerasi, E., Nesher, R. J. Biol. Chem. (1997) [Pubmed]
  13. C2 region-derived peptides inhibit translocation and function of beta protein kinase C in vivo. Ron, D., Luo, J., Mochly-Rosen, D. J. Biol. Chem. (1995) [Pubmed]
  14. The anti-inflammatory activity of estrogen in glial cells is regulated by the PKC-anchoring protein RACK-1. Viviani, B., Corsini, E., Binaglia, M., Lucchi, L., Galli, C.L., Marinovich, M. J. Neurochem. (2002) [Pubmed]
  15. Cellular adaptation to chronic ethanol results in altered compartmentalization and function of the scaffolding protein RACK1. Vagts, A.J., He, D.Y., Yaka, R., Ron, D. Alcohol. Clin. Exp. Res. (2003) [Pubmed]
  16. Functional impairment in protein kinase C by RACK1 (receptor for activated C kinase 1) deficiency in aged rat brain cortex. Pascale, A., Fortino, I., Govoni, S., Trabucchi, M., Wetsel, W.C., Battaini, F. J. Neurochem. (1996) [Pubmed]
  17. The dopamine D3 receptor is part of a homeostatic pathway regulating ethanol consumption. Jeanblanc, J., He, D.Y., McGough, N.N., Logrip, M.L., Phamluong, K., Janak, P.H., Ron, D. J. Neurosci. (2006) [Pubmed]
  18. Ontogenesis of protein kinase C betaII and its anchoring protein RACK1 in the maturation of alveolar macrophage functional responses. Corsini, E., Viviani, B., Lucchi, L., Marinovich, M., Racchi, M., Galli, C.L. Immunol. Lett. (2001) [Pubmed]
  19. Identification of the linker histone H1 as a protein kinase Cepsilon-binding protein in vascular smooth muscle. Zhao, M., Sutherland, C., Wilson, D.P., Deng, J., Macdonald, J.A., Walsh, M.P. Biochem. Cell Biol. (2004) [Pubmed]
  20. Subunit-specific association of protein kinase C and the receptor for activated C kinase with GABA type A receptors. Brandon, N.J., Uren, J.M., Kittler, J.T., Wang, H., Olsen, R., Parker, P.J., Moss, S.J. J. Neurosci. (1999) [Pubmed]
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