Gene Symbol: Cblb
Description: Cbl proto-oncogene B
Alias: E3 ubiquitin-protein ligase CBL-B, Cas-Br-M (murine) ecotropic retroviral transforming sequence b, Cas-Br-M (murine) ectropic retroviral transforming sequence b, Casitas B-lineage lymphoma b, Cbl proto-oncogene B, E3 ubiquitin protein ligase, Cbl proto-oncogene, E3 ubiquitin protein ligase B, RING-type E3 ubiquitin transferase CBL-B, SH3-binding protein CBL-B, casitas B-lineage lymphoma proto-oncogene b, signal transduction protein CBL-B
Species: rat
Products:     Cblb

Top Publications

  1. Thirone A, Carvalheira J, Hirata A, Velloso L, Saad M. Regulation of Cbl-associated protein/Cbl pathway in muscle and adipose tissues of two animal models of insulin resistance. Endocrinology. 2004;145:281-93 pubmed
    ..In addition, our data provide evidence that the CAP-Cbl pathway may have a role in the modulation of adiposity in fasting and in MSG-treated rats. ..
  2. Yokoi N, Komeda K, Wang H, Yano H, Kitada K, Saitoh Y, et al. Cblb is a major susceptibility gene for rat type 1 diabetes mellitus. Nat Genet. 2002;31:391-4 pubmed
    ..Here we report the positional cloning of Iddm/kdp1 and identify a nonsense mutation in Cblb, a member of the Cbl/Sli family of ubiquitin-protein ligases...
  3. Hirasaka K, Kohno S, Goto J, Furochi H, Mawatari K, Harada N, et al. Deficiency of Cbl-b gene enhances infiltration and activation of macrophages in adipose tissue and causes peripheral insulin resistance in mice. Diabetes. 2007;56:2511-22 pubmed
    ..Cbl-b is a negative regulator of macrophage infiltration and activation, and macrophage activation by Cbl-b deficiency contributes to the peripheral insulin resistance and glucose intolerance via cytokines secreted from macrophages. ..
  4. Krawczyk C, Bachmaier K, Sasaki T, Jones R, Snapper S, Bouchard D, et al. Cbl-b is a negative regulator of receptor clustering and raft aggregation in T cells. Immunity. 2000;13:463-73 pubmed
    ..Thus, Cbl-b functions as a negative regulator of receptor clustering and raft aggregation in T cells. ..
  5. Qu X, Sada K, Kyo S, Maeno K, Miah S, Yamamura H. Negative regulation of FcepsilonRI-mediated mast cell activation by a ubiquitin-protein ligase Cbl-b. Blood. 2004;103:1779-86 pubmed
    ..These results suggest that Cbl-b is a negative regulator of both Lyn-Syk-LAT and Gab2mediated complementary signaling pathways in FcepsilonRI-mediated mast cell activation. ..
  6. Kosoy R, Yokoi N, Seino S, Concannon P. Polymorphic variation in the CBLB gene in human type 1 diabetes. Genes Immun. 2004;5:232-5 pubmed
    b>CBLB was evaluated as a candidate gene for type 1 diabetes (T1D) susceptibility based on its association with autoimmunity in animal models and its role in T-cell costimulatory signaling...
  7. Yokoi N, Fujiwara Y, Wang H, Kitao M, Hayashi C, Someya T, et al. Identification and functional analysis of CBLB mutations in type 1 diabetes. Biochem Biophys Res Commun. 2008;368:37-42 pubmed publisher
    Casitas B-lineage lymphoma b (Cblb) is a negative regulator of T-cell activation and dysfunction of Cblb in rats and mice results in autoimmunity...
  8. Payne F, Smyth D, Pask R, Barratt B, Cooper J, Twells R, et al. Haplotype tag single nucleotide polymorphism analysis of the human orthologues of the rat type 1 diabetes genes Ian4 (Lyp/Iddm1) and Cblb. Diabetes. 2004;53:505-9 pubmed
    ..In the KDP rat, a nonsense mutation in the T-cell regulatory gene, Cblb, has been described as a major susceptibility locus...
  9. Heissmeyer V, Macian F, Im S, Varma R, Feske S, Venuprasad K, et al. Calcineurin imposes T cell unresponsiveness through targeted proteolysis of signaling proteins. Nat Immunol. 2004;5:255-65 pubmed
    ..Our results define a complex molecular program that links gene transcription induced by calcium and calcineurin to a paradoxical impairment of signal transduction in anergic T cells. ..

More Information


  1. Payne F, Cooper J, Walker N, Lam A, Smink L, Nutland S, et al. Interaction analysis of the CBLB and CTLA4 genes in type 1 diabetes. J Leukoc Biol. 2007;81:581-3 pubmed
    ..Recently, evidence of a statistical interaction between polymorphisms in two negative immunoregulatory genes, CBLB and CTLA4, has been reported in type 1 diabetes (T1D)...
  2. Bergholdt R, Taxvig C, Eising S, Nerup J, Pociot F. CBLB variants in type 1 diabetes and their genetic interaction with CTLA4. J Leukoc Biol. 2005;77:579-85 pubmed
    ..of an animal model of T1D, the Komeda diabetes-prone rat, have demonstrated that the Casitas-B-lineage lymphoma b (cblb) gene is a major susceptibility gene in the development of diabetes and other autoimmune features of this rat...
  3. Kyo S, Sada K, Qu X, Maeno K, Miah S, Kawauchi Kamata K, et al. Negative regulation of Lyn protein-tyrosine kinase by c-Cbl ubiquitin-protein ligase in Fc epsilon RI-mediated mast cell activation. Genes Cells. 2003;8:825-36 pubmed
    ..Targeting of c-Cbl in the lipid raft results in the inhibition of Fc epsilon RI-mediated mast cell activation. ..
  4. Xu Z, George C, Jolly C. CD28 activation does not down-regulate Cbl-b expression in aged rat T-lymphocytes. Mech Ageing Dev. 2004;125:595-602 pubmed
    ..These data provide evidence for a novel mechanism by which aging reduces T-lymphocyte function. ..
  5. Qu X, Miah S, Hatani T, Okazaki M, Hori Tamura N, Yamamura H, et al. Selective inhibition of Fcepsilon RI-mediated mast cell activation by a truncated variant of Cbl-b related to the rat model of type 1 diabetes mellitus. J Biochem. 2005;137:711-20 pubmed
    ..These structural and functional analyses reveal the mechanism underlying the selective inhibition of cellular signaling by the truncated variant of Cbl-b related to insulin-dependent diabetes mellitus. ..
  6. Carpino N, Turner S, Mekala D, Takahashi Y, Zang H, Geiger T, et al. Regulation of ZAP-70 activation and TCR signaling by two related proteins, Sts-1 and Sts-2. Immunity. 2004;20:37-46 pubmed
    ..Therefore, Sts-1 and Sts-2 are critical regulators of the signaling pathways that regulate T cell activation. ..
  7. Adriaansen J, Kuhlman R, van Holten J, Kaynor C, Vervoordeldonk M, Tak P. Intraarticular interferon-beta gene therapy ameliorates adjuvant arthritis in rats. Hum Gene Ther. 2006;17:985-96 pubmed
    ..Local overexpression of IFN-beta inhibits arthritis progression and protects against bone destruction in rat AA. These findings validate IFN-beta as a therapeutic molecule for intraarticular gene therapy of arthritis. ..
  8. Nikawa T, Ishidoh K, Hirasaka K, Ishihara I, Ikemoto M, Kano M, et al. Skeletal muscle gene expression in space-flown rats. FASEB J. 2004;18:522-4 pubmed
  9. Nishio H, Otsuka M, Kinoshita S, Tokuoka T, Nakajima M, Noda Y, et al. Phosphorylation of c-Cbl protooncogene product following ethanol administration in rat cerebellum: possible involvement of Fyn kinase. Brain Res. 2002;950:203-9 pubmed
    ..These findings indicate that Cbl is tyrosine-phosphorylated in rat cerebellum in response to ethanol administration, and also raise the possibility that Fyn kinase may be involved in the process. ..
  10. Nakao R, Hirasaka K, Goto J, Ishidoh K, Yamada C, Ohno A, et al. Ubiquitin ligase Cbl-b is a negative regulator for insulin-like growth factor 1 signaling during muscle atrophy caused by unloading. Mol Cell Biol. 2009;29:4798-811 pubmed publisher
    ..The inhibition of Cbl-b-mediated ubiquitination may be a new therapeutic strategy for unloading-mediated muscle atrophy. ..
  11. Ohrt T, Mancini A, Tamura T, Niedenthal R. c-Cbl binds to tyrosine-phosphorylated neurotrophin receptor p75 and induces its ubiquitination. Cell Signal. 2004;16:1291-8 pubmed
    ..This interaction is a prerequisite for ubiquitination of p75NTR. Our data suggest a c-Cbl-dependent ubiquitination of p75NTR involved in the regulation of p75NTR signalling. ..
  12. Qu X, Li Y, Liu J, Xu L, Zhang Y, Hu X, et al. Cbl-b promotes chemotherapy-induced apoptosis in rat basophilic leukemia cells by suppressing PI3K/Akt activation and enhancing MEK/ERK activation. Mol Cell Biochem. 2010;340:107-14 pubmed publisher
    ..The consistent results were also showed in the process of Ara-c treatment. These observations indicate that Cbl-b promotes RBL-2H3 apoptosis induced by VP-16 or Ara-c, probably through inhibition of Akt and activation of ERK. ..