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

• Quantitative immunoblotting revealed that RACK1 content was decreased by approximately 50% in aged rat brain cortex, compared with that in adult and middle-aged animals [16].
• Immunohistochemistry was implemented to visualize the localization of RACK1 and to monitor the protein level of c-fos [15].
• Although of similar molecular weight to RACK-1, a known PKCepsilon-binding protein, these proteins were separated from RACK-1 by SDS-PAGE and differential NaCl extraction and were not recognized by an antibody to RACK-1 [19].
• Using immunoprecipitation, the association of PKC isoforms and RACK-1 with neuronal GABA(A) receptors was seen [20].

References