Disease relevance of GNB2L1

• We also show that down-regulation of RACK1 by short interfering RNA inhibits growth and stimulates prostate-specific antigen transcription in androgen-treated prostate cancer cells [1].
• PDE4D5 and RACK1 interacted with high affinity (Ka approximately 7 nM) [corrected] when they were expressed and purified from Escherichia coli, demonstrating that the interaction does not require intermediate proteins [2].
• We demonstrate that RACK1 interacts with PTPmu when co-expressed in a recombinant baculovirus expression system [3].
• Protein kinase C epsilon-dependent regulation of cystic fibrosis transmembrane regulator involves binding to a receptor for activated C kinase (RACK1) and RACK1 binding to Na+/H+ exchange regulatory factor [4].
• Furthermore, RACK1 interacted with mumps virus V protein with a higher affinity than STAT-1 did [5].
• The significance of this work lies in the discovery of a mechanism by which the growth of colon cancer cells can be slowed, by RACK1 suppression of an oncogenic kinase at critical cell cycle checkpoints [6].

Psychiatry related information on GNB2L1

• Increased association of brain protein kinase C with the receptor for activated C kinase-1 (RACK1) in bipolar affective disorder [7].
• Moreover, human studies have shown that PKC and its adaptor protein RACK1 are also interdependent in pathological brain aging (e.g., Alzheimer's disease); in fact, calcium-dependent PKC translocation and RACK1 levels are both deficient in an area-selective manner [8].
• This study examined whether dyslexic children learning to read German show the same nonword reading deficit, which is characteristic of dyslexic children learning to read English (Rack, Olson, & Snowling, 1992), a deficit which is taken as evidence for a phonological impairment underlying dyslexia [9].

High impact information on GNB2L1

• RACK1 competes with HSP90 for binding to the PAS-A domain of HIF-1alpha in vitro and in human cells [10].
• In finding the role of RACK1 in activation of JNK by PKC, our study also highlights the nature of crosstalk between these two signal-transduction pathways [11].
• Forced expression of RACK1, which is the plectin-binding receptor protein for activated PKCdelta, in wild-type keratinocytes elevated their migration potential close to that of plectin-null cells [12].
• MURF1 interacts with receptor for activated protein kinase C (RACK1) and colocalizes with RACK1 after activation with phenylephrine or PMA [13].
• Consistent with these data, PKCalpha along with the PKC binding protein RACK1 are immunoprecipitated with wild-type P0, and inhibition of PKC activity abolishes P0-mediated adhesion [14].

Chemical compound and disease context of GNB2L1

• Immunoprecipitation and glutathione S-transferase pull-down experiments revealed that the association of RACK1 or mumps virus V protein with the IFN receptor was undetectable in mumps virus-infected cells [5].

Biological context of GNB2L1

• During a large-scale screen of a human fetal brain cDNA library, a novel human gene GNB2L1 encoding a novel RACK (receptor of activated protein kinase C) protein was isolated and sequenced [15].
• We also observed RACK1 to suppress ligand-dependent and -independent AR transactivation through PKC activation [16].
• We show here sequestering of receptor for activated C kinase 1 (RACK1) to the cytoskeleton through the cytoskeletal linker protein plectin during the initial stages of cell adhesion [17].
• Our results also demonstrate binding of NHERF to RACK1 at the WD5 repeat, which is distinct from the PKCepsilon binding site on the WD6 repeat of RACK1 [18].
• PKC stimulation led to eIF6 phosphorylation, and mutation of a serine residue in the carboxy terminus of eIF6 impaired RACK1/PKC-mediated translational rescue [19].

Anatomical context of GNB2L1

• Colocalization studies in transfected cells suggest that TNF-R55 forms a complex with FAN and that this complex recruits RACK1 to the plasma membrane [20].
• The interaction of FAN and RACK1 was verified in vitro by glutathione S-transferase-based coprecipitation assays as well as in eukaryotic cells by coimmunoprecipitation experiments [20].
• RACK1 is a major component of translating ribosomes, which harbour significant amounts of PKC [19].
• A cDNA probe for one of these genes, probe C12.3 isolated from a chicken liver cDNA library, was used to clone the homologous sequence H12.3 from a human B-lymphoblastoid cell line cDNA library [21].
• Overexpression of RACK1 also led to enhanced cell spreading, increased stress fibers, and increased focal adhesions, which were accompanied by increased tyrosine phosphorylation of focal adhesion kinase and paxillin [22].

Associations of GNB2L1 with chemical compounds

• Tyrosine phosphorylation on many cellular proteins decreased in 293T cells that transiently overexpressed RACK1 [23].
• We provide novel evidence that the scaffolding protein RACK1 mediates the interaction between integrin beta chain and activated PKCepsilon [24].
• UV/DECA treatment of synthetic peptides modeled after the RACK-1-binding site in the C2 region of PKC beta induced modification of Ser218-Leu-Asn-Pro-Glu-Trp-Asn-Glu-Thr226, but not of a control peptide [25].
• The WD-repeat protein receptor for activated C-kinase (RACK1) was identified by its interaction with the cyclic AMP-specific phosphodiesterase (PDE4) isoform PDE4D5 in a yeast two-hybrid screen [2].
• Photoinduced inactivation of protein kinase C by dequalinium identifies the RACK-1-binding domain as a recognition site [25].
• Taken together, the data demonstrate that Tyr-302 in RACK1 is required for interaction with PP2A and beta1 integrin, for regulation of PP2A activity, and for IGF-I-mediated cell migration and proliferation [26].

Physical interactions of GNB2L1

• The scaffolding protein RACK1 interacts with androgen receptor and promotes cross-talk through a protein kinase C signaling pathway [16].
• Furthermore, eIF6 interacts in the cytoplasm with RACK1, a receptor for activated protein kinase C (PKC) [19].
• In a cytokine signaling cascade, Rack-1 has been reported to interact with the IFN-alphabeta receptor and Stat1 [27].
• RACK1 also interacted with the IGF-1R in fibroblasts and MCF-7 cells and with endogenous insulin receptor in COS cells [28].
• Rack-1 interacts weakly with the kinase domain and interacts strongly with the pseudokinase domain of Tyk2 [27].

Regulatory relationships of GNB2L1

• Overexpression of RACK1 in either R+ fibroblasts or MCF-7 cells inhibited IGF-1-induced phosphorylation of Akt, whereas it enhanced phosphorylation of Erks and Jnks [28].
• One of protein kinase C (PKC) isozymes, PKC beta binds to receptor for activated C kinase 1 (RACK1), and their complex is suggested to be translocated to melanosomes [29].
• A strategy of mutagenesis followed by yeast two-hybrid assay was used to determine the sites on the WD-repeat protein Receptor for Activated C Kinase 1 (RACK1) necessary for it to interact with the cAMP-specific phosphodiesterase isoform PDE4D5 [30].
• CONCLUSIONS: RACK1 mediated translocation of activated PKCalpha to the cell membrane and modulation of integrin-associated signaling are likely to be important in regulation of downstream signaling cascades controlling chondrocyte responses to mechanical stimuli [31].
• The ubiquitination and degradation of HIF-1alpha are promoted by RACK1 [32].
• Our data reveal a novel mechanism whereby IGF-I and c-Abl control RACK1 association with FAK to facilitate adhesion signaling [33].

Other interactions of GNB2L1

• In this report we found that RACK1, which was previously shown to be a protein kinase C (PKC)-anchoring protein that determines the localization of activated PKCbetaII isoform, facilitates ligand-independent AR nuclear translocation upon PKC activation by indolactam V [16].
• In the IFN system, RACK-1 functions as an adaptor recruiting the transcription factor STAT1 to the receptor complex [34].
• The WD motif-containing protein RACK-1 functions as a scaffold protein within the type I IFN receptor-signaling complex [34].
• Finally, we provide evidence that RACK-1 may also serve as a scaffold protein in other cytokine systems such as IL-2, IL-4, and erythropoietin [34].
• We propose that eIF6 release regulates subunit joining, and that RACK1 provides a physical and functional link between PKC signalling and ribosome activation [19].

Analytical, diagnostic and therapeutic context of GNB2L1

• The interaction was confirmed by co-immunoprecipitation of native RACK1 and PDE4D5 from COS7, HEK293, 3T3-F442A, and SK-N-SH cell lines [2].
• However, stimulation of cells with either IFN-beta1b or PMA did result in an increase in detectable immunofluorescence and intracellular redistribution of RACK-1 [35].
• The WD motif-containing protein receptor for activated protein kinase C (RACK1) is required for recruitment and activation of signal transducer and activator of transcription 1 through the type I interferon receptor [36].
• Immunofluorescence and confocal microscopy of RACK1 and CFTR revealed colocalization of the proteins to the apical and lateral regions of Calu-3 cells [4].
• METHODS: Primary cultures of human articular chondrocytes and a human chondrocyte cell line were studied for expression of PKC isozymes and RACK1 by western blotting [31].

References