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Gene Review

GNB2L1  -  guanine nucleotide binding protein (G...

Homo sapiens

Synonyms: Cell proliferation-inducing gene 21 protein, Gnb2-rs1, Guanine nucleotide-binding protein subunit beta-2-like 1, Guanine nucleotide-binding protein subunit beta-like protein 12.3, H12.3, ...
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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


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


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


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


  1. Receptor for Activated C Kinase 1 (RACK1) and Src Regulate the Tyrosine Phosphorylation and Function of the Androgen Receptor. Kraus, S., Gioeli, D., Vomastek, T., Gordon, V., Weber, M.J. Cancer Res. (2006) [Pubmed]
  2. The RACK1 signaling scaffold protein selectively interacts with the cAMP-specific phosphodiesterase PDE4D5 isoform. Yarwood, S.J., Steele, M.R., Scotland, G., Houslay, M.D., Bolger, G.B. J. Biol. Chem. (1999) [Pubmed]
  3. The PTPmu protein-tyrosine phosphatase binds and recruits the scaffolding protein RACK1 to cell-cell contacts. Mourton, T., Hellberg, C.B., Burden-Gulley, S.M., Hinman, J., Rhee, A., Brady-Kalnay, S.M. J. Biol. Chem. (2001) [Pubmed]
  4. 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. Liedtke, C.M., Yun, C.H., Kyle, N., Wang, D. J. Biol. Chem. (2002) [Pubmed]
  5. Association of mumps virus V protein with RACK1 results in dissociation of STAT-1 from the alpha interferon receptor complex. Kubota, T., Yokosawa, N., Yokota, S., Fujii, N. J. Virol. (2002) [Pubmed]
  6. RACK1 inhibits colonic cell growth by regulating Src activity at cell cycle checkpoints. Mamidipudi, V., Dhillon, N.K., Parman, T., Miller, L.D., Lee, K.C., Cartwright, C.A. Oncogene (2007) [Pubmed]
  7. Increased association of brain protein kinase C with the receptor for activated C kinase-1 (RACK1) in bipolar affective disorder. Wang, H., Friedman, E. Biol. Psychiatry (2001) [Pubmed]
  8. Protein kinase C signal transduction regulation in physiological and pathological aging. Battaini, F., Pascale, A. Ann. N. Y. Acad. Sci. (2005) [Pubmed]
  9. The nonword reading deficit in developmental dyslexia: evidence from children learning to read German. Wimmer, H. Journal of experimental child psychology. (1996) [Pubmed]
  10. RACK1 competes with HSP90 for binding to HIF-1alpha and is required for O(2)-independent and HSP90 inhibitor-induced degradation of HIF-1alpha. Liu, Y.V., Baek, J.H., Zhang, H., Diez, R., Cole, R.N., Semenza, G.L. Mol. Cell (2007) [Pubmed]
  11. RACK1 mediates activation of JNK by protein kinase C [corrected]. López-Bergami, P., Habelhah, H., Bhoumik, A., Zhang, W., Wang, L.H., Ronai, Z. Mol. Cell (2005) [Pubmed]
  12. Plectin-controlled keratin cytoarchitecture affects MAP kinases involved in cellular stress response and migration. Osmanagic-Myers, S., Gregor, M., Walko, G., Burgstaller, G., Reipert, S., Wiche, G. J. Cell Biol. (2006) [Pubmed]
  13. Muscle ring finger protein-1 inhibits PKC{epsilon} activation and prevents cardiomyocyte hypertrophy. Arya, R., Kedar, V., Hwang, J.R., McDonough, H., Li, H.H., Taylor, J., Patterson, C. J. Cell Biol. (2004) [Pubmed]
  14. Mutations in the cytoplasmic domain of P0 reveal a role for PKC-mediated phosphorylation in adhesion and myelination. Xu, W., Shy, M., Kamholz, J., Elferink, L., Xu, G., Lilien, J., Balsamo, J. J. Cell Biol. (2001) [Pubmed]
  15. Cloning, expression and genomic structure of a novel human GNB2L1 gene, which encodes a receptor of activated protein kinase C (RACK). Wang, S., Chen, J.Z., Zhang, Z., Gu, S., Ji, C., Tang, R., Ying, K., Xie, Y., Mao, Y. Mol. Biol. Rep. (2003) [Pubmed]
  16. The scaffolding protein RACK1 interacts with androgen receptor and promotes cross-talk through a protein kinase C signaling pathway. Rigas, A.C., Ozanne, D.M., Neal, D.E., Robson, C.N. J. Biol. Chem. (2003) [Pubmed]
  17. Plectin-RACK1 (receptor for activated C kinase 1) scaffolding: a novel mechanism to regulate protein kinase C activity. Osmanagic-Myers, S., Wiche, G. J. Biol. Chem. (2004) [Pubmed]
  18. The N-terminus of the WD5 repeat of human RACK1 binds to airway epithelial NHERF1. Liedtke, C.M., Wang, X. Biochemistry (2006) [Pubmed]
  19. Release of eIF6 (p27BBP) from the 60S subunit allows 80S ribosome assembly. Ceci, M., Gaviraghi, C., Gorrini, C., Sala, L.A., Offenhäuser, N., Marchisio, P.C., Biffo, S. Nature (2003) [Pubmed]
  20. Interaction with factor associated with neutral sphingomyelinase activation, a WD motif-containing protein, identifies receptor for activated C-kinase 1 as a novel component of the signaling pathways of the p55 TNF receptor. Tcherkasowa, A.E., Adam-Klages, S., Kruse, M.L., Wiegmann, K., Mathieu, S., Kolanus, W., Krönke, M., Adam, D. J. Immunol. (2002) [Pubmed]
  21. Physical linkage of a guanine nucleotide-binding protein-related gene to the chicken major histocompatibility complex. Guillemot, F., Billault, A., Auffray, C. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  22. RACK1, an insulin-like growth factor I (IGF-I) receptor-interacting protein, modulates IGF-I-dependent integrin signaling and promotes cell spreading and contact with extracellular matrix. Hermanto, U., Zong, C.S., Li, W., Wang, L.H. Mol. Cell. Biol. (2002) [Pubmed]
  23. RACK1, a receptor for activated C kinase and a homolog of the beta subunit of G proteins, inhibits activity of src tyrosine kinases and growth of NIH 3T3 cells. Chang, B.Y., Conroy, K.B., Machleder, E.M., Cartwright, C.A. Mol. Cell. Biol. (1998) [Pubmed]
  24. The anchoring protein RACK1 links protein kinase Cepsilon to integrin beta chains. Requirements for adhesion and motility. Besson, A., Wilson, T.L., Yong, V.W. J. Biol. Chem. (2002) [Pubmed]
  25. Photoinduced inactivation of protein kinase C by dequalinium identifies the RACK-1-binding domain as a recognition site. Rotenberg, S.A., Sun, X.G. J. Biol. Chem. (1998) [Pubmed]
  26. Tyrosine 302 in RACK1 is essential for insulin-like growth factor-I-mediated competitive binding of PP2A and beta1 integrin and for tumor cell proliferation and migration. Kiely, P.A., Baillie, G.S., Lynch, M.J., Houslay, M.D., O'Connor, R. J. Biol. Chem. (2008) [Pubmed]
  27. Tyrosine kinase 2 interacts with and phosphorylates receptor for activated C kinase-1, a WD motif-containing protein. Haro, T., Shimoda, K., Kakumitsu, H., Kamezaki, K., Numata, A., Ishikawa, F., Sekine, Y., Muromoto, R., Matsuda, T., Harada, M. J. Immunol. (2004) [Pubmed]
  28. RACK1 is an insulin-like growth factor 1 (IGF-1) receptor-interacting protein that can regulate IGF-1-mediated Akt activation and protection from cell death. Kiely, P.A., Sant, A., O'Connor, R. J. Biol. Chem. (2002) [Pubmed]
  29. Conformational analysis in solution of protein kinase C betaII V5-1 peptide. Shin, C., Ahn, J.H., Lim, Y. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  30. Identification of a surface on the beta-propeller protein RACK1 that interacts with the cAMP-specific phosphodiesterase PDE4D5. Steele, M.R., McCahill, A., Thompson, D.S., MacKenzie, C., Isaacs, N.W., Houslay, M.D., Bolger, G.B. Cell. Signal. (2001) [Pubmed]
  31. Activation of Integrin-RACK1/PKCalpha signalling in human articular chondrocyte mechanotransduction. Lee, H.S., Millward-Sadler, S.J., Wright, M.O., Nuki, G., Al-Jamal, R., Salter, D.M. Osteoarthr. Cartil. (2002) [Pubmed]
  32. RACK1 vs. HSP90: competition for HIF-1alpha degradation vs. stabilization. Liu, Y.V., Semenza, G.L. Cell Cycle (2007) [Pubmed]
  33. Phosphorylation of RACK1 on tyrosine 52 by c-Abl is required for insulin-like growth factor I-mediated regulation of focal adhesion kinase. Kiely, P.A., Baillie, G.S., Barrett, R., Buckley, D.A., Adams, D.R., Houslay, M.D., O'Connor, R. J. Biol. Chem. (2009) [Pubmed]
  34. The WD motif-containing protein RACK-1 functions as a scaffold protein within the type I IFN receptor-signaling complex. Usacheva, A., Tian, X., Sandoval, R., Salvi, D., Levy, D., Colamonici, O.R. J. Immunol. (2003) [Pubmed]
  35. Receptor for activated C-kinase (RACK-1), a WD motif-containing protein, specifically associates with the human type I IFN receptor. Croze, E., Usacheva, A., Asarnow, D., Minshall, R.D., Perez, H.D., Colamonici, O. J. Immunol. (2000) [Pubmed]
  36. 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. Usacheva, A., Smith, R., Minshall, R., Baida, G., Seng, S., Croze, E., Colamonici, O. J. Biol. Chem. (2001) [Pubmed]
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