High impact information on Gnb2l1

• The early CD4(+) T cell response in these mice is oligoclonal and reflects the expansion of Vbeta4/ Valpha8-bearing T cells in response to a single epitope from the parasite Leishmania homologue of mammalian RACK1 (LACK) antigen [1].
• The integrin-tetraspanin complex affects epithelial cell-cell adhesion at the level of gene expression both by regulating expression of PTPmu and by organizing a multimolecular complex containing PKCbetaII, RACK1, PTPmu, beta-catenin, and E-cadherin [2].
• Here, we report that, in mice, the stress-induced splice variant of acetylcholinesterase, AChE-R, interacts intraneuronally with the scaffold protein RACK1 and through it, with its target, protein kinase CbetaII (PKCbetaII), which is known to be involved in fear conditioning [3].
• Interaction of "readthrough" acetylcholinesterase with RACK1 and PKCbeta II correlates with intensified fear-induced conflict behavior [3].
• Insulin-like growth factor I controls a mutually exclusive association of RACK1 with protein phosphatase 2A and beta1 integrin to promote cell migration [4].

Biological context of Gnb2l1

• In order to gain insight into the neurological functions of RACK1, we examined the expression of RACK1 mRNA and protein during gestation and in the adult mouse brain [5].
• HiTrap-syndecan-2/p120-GAP and HiTrap-syndecan-2/RACK1 affinity columns were applied to reveal that Src tyrosine kinase was highly expressed in BALB/3T3 cells transfected with plasmids pcDNA3.1-[S-ras(Q(61)K)] of shrimp Penaeus japonicus [6].
• The interaction of Src and RACK1 is enhanced by activation of protein kinase C and tyrosine phosphorylation of RACK1 [7].
• RACK1, via its association with these protein kinases, may play a key role in signal transduction [7].
• Here we have mapped the RACK1 binding sites on G betagamma [8].

Anatomical context of Gnb2l1

• We found that betaIIPKC had a much more restricted expression pattern than RACK1 and overlapped with the scaffolding protein only in certain regions, including the CA1 area of the hippocampus, cerebellum and striatum [5].
• Subcellular staining was detected mainly in the cell bodies and extending into dendrites, whereas RACK1 was not present significantly in axonal fibers or nuclei [5].
• At E13.5, RACK1 is most abundant in the telencephalon [5].
• RACK1 is a multifunctional scaffolding protein known to be involved in the regulation of various signaling cascades in the central nervous system (CNS) [5].
• At E18.5, RACK1 is expressed most abundantly in layers 1-4 of the cortex, striatum, hippocampus, dentate gyrus and specific thalamic nuclei [5].

Associations of Gnb2l1 with chemical compounds

• The WD repeat scaffolding protein RACK1 can mediate integration of the insulin-like growth factor I receptor (IGF-IR) and integrin signaling in transformed cells [4].
• The serine threonine phosphatase protein phosphatase 2A (PP2A) was found associated with RACK1 in serum-starved cells, and it dissociated immediately upon stimulation with IGF-I [4].
• RACK1 is an intracellular receptor for the serine/ threonine protein kinase C. Previously, we demonstrated that RACK1 also interacts with the Src protein-tyrosine kinase [7].
• In vivo exposure to ethanol caused RACK1 to localize to nuclei in specific brain regions, but did not affect the compartmentalization of betaIIPKC [9].
• The results also demonstrate that rasagiline treatment significantly elevated the levels of phosphorylated myristoylated alanine-rich C kinase substrate (p-MARCKS), a major substrate for PKC, as well as the levels of receptors for activated C kinase 1 (RACK1) [10].

Physical interactions of Gnb2l1

• On the other hand, the syndecan-2/RACK1 complex was found to have Src in an inactivated form [11].
• The selective affinity between p120-GAP and syndecan-2 was found to be sufficient to detach RACK1 [11].
• RACK1 binds to a signal transfer region of G betagamma and inhibits phospholipase C beta2 activation [8].
• We found that RACK1 interacts with several different G betagamma isoforms, including G beta1gamma1, Gbeta1gamma2, and Gbeta5gamma2, with similar affinities, suggesting that the conserved residues between G beta1 and G beta5 may be involved in their binding to RACK1 [8].

Co-localisations of Gnb2l1

• Upon activation of PKC, RACK1 co-localizes with the Src tyrosine kinase at the plasma membrane and functions as a substrate, binding partner and inhibitor of Src (as measured in vitro), and a growth inhibitor in NIH 3T3 cells [12].

Regulatory relationships of Gnb2l1

• RACK1 inhibits Src-mediated p190RhoGAP signaling and actin cytoskeleton rearrangement [12].
• Previously, we showed that RACK1 inhibits c-Src kinase activity and NIH3T3 cell growth [13].
• Expression of a peptide binding to receptor for activated C-kinase (RACK1) inhibits phorbol myristoyl acetate-stimulated phospholipase D activity in C3H/10T1/2 cells: dissociation of phospholipase D-mediated phosphatidylcholine breakdown from its synthesis [14].

Other interactions of Gnb2l1

• On the other hand, in the absence of syndecan-2, GTP-K(B)-Ras(Q(61)K) was found to react with RACK1 [6].
• In the adult mouse, RACK1 is ubiquitously expressed in neuronal perikarya in most brain regions, with relatively higher levels in hippocampus, olfactory bulb, cortex and cerebellum [5].
• To address the mechanism of RACK1 function, we searched for regulatory proteins that associate with RACK1 in an IGF-I-dependent manner [4].
• This suggests that integrin ligation displaces PP2A from RACK1 [4].
• In GV oocytes, PKC-alpha, PKC-betaII, and RACK1 were uniformly distributed in the cytoplasm, while PKC-betaI was localized in the cytoplasm and in the plasma membrane as well [15].

Analytical, diagnostic and therapeutic context of Gnb2l1

• In situ hybridization revealed that p205 mRNA is strongly and ubiquitously expressed in the embryonic and early postnatal mouse brain [16].
• Developmental Northern blot analysis revealed that a p205 mRNA is expressed at high levels in the embryonic mouse brain, decreasing as development proceeds [16].
• In nonhematopoietic cell lines, p205 and p204 expression inhibited NIH3T3 cell colony formation in vitro, and microinjection of p205 expression vectors into NIH3T3 fibroblasts inhibited serum-induced proliferation [17].
• Northern and Western blot analyses showed that p205 was ubiquitously expressed in all the rat tissues examined, whereas p190 was specifically expressed in brain [18].
• Here, using semiquantitative immunocytochemistry and confocal microscopy we analyze the relative amount and subcellular distribution of ten isozymes of PKC (alpha, betaI, betaII, gamma, delta, epsilon, eta, theta, zeta, iota/lambda) and a PKC-anchoring protein, receptor for activated C-kinase 1 (RACK1) [19].

References