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Gene Review

Bcar1  -  breast cancer anti-estrogen resistance 1

Rattus norvegicus

Synonyms: Breast cancer anti-estrogen resistance protein 1, CRK-associated substrate, Cas, Crkas, P130CAS, ...
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Disease relevance of Bcar1

  • The large (130kDa), multi-domain Cas molecule contains an SH3 domain, a Src-binding domain, a serine-rich protein interaction region, and a C-terminal region that participates in protein interactions implicated in antiestrogen resistance in breast cancer [1].
  • These results demonstrated that Cas functions as a molecule promoting cell movement, cell migration, and cell spreading and suggest that Cas would be implicated in various physiological and pathological processes, such as would healing, chemotaxis, and tumor invasion [2].

High impact information on Bcar1


Biological context of Bcar1


Anatomical context of Bcar1


Associations of Bcar1 with chemical compounds

  • Mutation of this tyrosine to glutamic acid, but not to phenylalanine, disrupts Cas binding to SHEP1 without inhibiting Ras GTPase binding [14].
  • This study reports the first structure of a functional domain of Cas. The solution structure of the serine-rich region has been determined by NMR spectroscopy, demonstrating that this is a stable domain that folds as a four-helix bundle, a protein-interaction motif [11].
  • SHEP1 is a signaling protein that contains a guanine nucleotide exchange factor-like domain, which binds Ras family GTPases and also forms a stable complex with the scaffolding protein Crk-associated substrate (Cas) [14].
  • Together, these results show that the identity of the previously described p125 beta-cell protein is Cas and that Cas undergoes rapid glucose-induced tyrosine phosphorylation in beta-cells [12].
  • The protein products are soluble, homogeneous, monodisperse, and highly suitable for structural studies to define the role of Cas in integrin-mediated cell signaling [1].

Physical interactions of Bcar1

  • The C-terminal Src-binding domain played essential roles in cell migration and membrane localization of Cas, although it was dispensable in the organization of actin stress fibers [7].

Regulatory relationships of Bcar1


Other interactions of Bcar1


Analytical, diagnostic and therapeutic context of Bcar1

  • Finally, it is also demonstrated via Western blotting that Cas is present in normal isolated rat islets [12].
  • Western and immunohistochemistry analyses validated the presence of CAS in the aorta, and tissue bath experiments demonstrated reduction of contraction to 5-HT (13.5 +/- 5% control maximum) and the 5-HT(2) receptor agonist alpha-methyl-5-HT (6 +/- 2% maximum) by latrunculin B (10(-6) mol/l), an actin disruptor [17].
  • Sequence analysis showed that Cas contains 10 DXXD consensus sites preferred by caspase-3 [18].
  • Further, we found by immunoprecipitation experiments that the 120 kDa protein was p130cas, a crk-associated src substrate [19].


  1. Organization of functional domains in the docking protein p130Cas. Nasertorabi, F., Garcia-Guzman, M., Briknarová, K., Larsen, E., Havert, M.L., Vuori, K., Ely, K.R. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  2. p130(Cas), an assembling molecule of actin filaments, promotes cell movement, cell migration, and cell spreading in fibroblasts. Honda, H., Nakamoto, T., Sakai, R., Hirai, H. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  3. Structure and function of Cas-L, a 105-kD Crk-associated substrate-related protein that is involved in beta 1 integrin-mediated signaling in lymphocytes. Minegishi, M., Tachibana, K., Sato, T., Iwata, S., Nojima, Y., Morimoto, C. J. Exp. Med. (1996) [Pubmed]
  4. A novel signaling molecule, p130, forms stable complexes in vivo with v-Crk and v-Src in a tyrosine phosphorylation-dependent manner. Sakai, R., Iwamatsu, A., Hirano, N., Ogawa, S., Tanaka, T., Mano, H., Yazaki, Y., Hirai, H. EMBO J. (1994) [Pubmed]
  5. Paxillin alpha and Crk-associated substrate exert opposing effects on cell migration and contact inhibition of growth through tyrosine phosphorylation. Yano, H., Uchida, H., Iwasaki, T., Mukai, M., Akedo, H., Nakamura, K., Hashimoto, S., Sabe, H. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  6. Introduction of p130cas signaling complex formation upon integrin-mediated cell adhesion: a role for Src family kinases. Vuori, K., Hirai, H., Aizawa, S., Ruoslahti, E. Mol. Cell. Biol. (1996) [Pubmed]
  7. Differential regulation of cell migration, actin stress fiber organization, and cell transformation by functional domains of Crk-associated substrate. Huang, J., Hamasaki, H., Nakamoto, T., Honda, H., Hirai, H., Saito, M., Takato, T., Sakai, R. J. Biol. Chem. (2002) [Pubmed]
  8. Phosphorylation-dependent cleavage of p130cas in apoptotic rat-1 cells. Hoon Kim, D., Jeon Choi, S., Kook, S., Kim, W., Keun Song, W. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  9. Integrin-mediated cell adhesion promotes tyrosine phosphorylation of p130Cas, a Src homology 3-containing molecule having multiple Src homology 2-binding motifs. Nojima, Y., Morino, N., Mimura, T., Hamasaki, K., Furuya, H., Sakai, R., Sato, T., Tachibana, K., Morimoto, C., Yazaki, Y. J. Biol. Chem. (1995) [Pubmed]
  10. Processive phosphorylation of p130Cas by Src depends on SH3-polyproline interactions. Pellicena, P., Miller, W.T. J. Biol. Chem. (2001) [Pubmed]
  11. The serine-rich domain from Crk-associated substrate (p130cas) is a four-helix bundle. Briknarová, K., Nasertorabi, F., Havert, M.L., Eggleston, E., Hoyt, D.W., Li, C., Olson, A.J., Vuori, K., Ely, K.R. J. Biol. Chem. (2005) [Pubmed]
  12. Glucose stimulates the tyrosine phosphorylation of Crk-associated substrate in pancreatic beta-cells. Konrad, R.J., Gold, G., Lee, T.N., Workman, R., Broderick, C.L., Knierman, M.D. J. Biol. Chem. (2003) [Pubmed]
  13. Focal adhesion kinase and p130Cas mediate both sarcomeric organization and activation of genes associated with cardiac myocyte hypertrophy. Kovacic-Milivojević, B., Roediger, F., Almeida, E.A., Damsky, C.H., Gardner, D.G., Ilić, D. Mol. Biol. Cell (2001) [Pubmed]
  14. SHEP1 function in cell migration is impaired by a single amino acid mutation that disrupts association with the scaffolding protein cas but not with Ras GTPases. Dail, M., Kalo, M.S., Seddon, J.A., Côté, J.F., Vuori, K., Pasquale, E.B. J. Biol. Chem. (2004) [Pubmed]
  15. Src and Cas are essentially but differentially involved in angiotensin II-stimulated migration of vascular smooth muscle cells via extracellular signal-regulated kinase 1/2 and c-Jun NH2-terminal kinase activation. Kyaw, M., Yoshizumi, M., Tsuchiya, K., Kagami, S., Izawa, Y., Fujita, Y., Ali, N., Kanematsu, Y., Toida, K., Ishimura, K., Tamaki, T. Mol. Pharmacol. (2004) [Pubmed]
  16. Protein tyrosine phosphatase 1B negatively regulates integrin signaling. Liu, F., Sells, M.A., Chernoff, J. Curr. Biol. (1998) [Pubmed]
  17. A new signaling paradigm for serotonin: use of Crk-associated substrate in arterial contraction. Ogden, K., Thompson, J.M., Hickner, Z., Huang, T., Tang, D.D., Watts, S.W. Am. J. Physiol. Heart Circ. Physiol. (2006) [Pubmed]
  18. Caspase-mediated cleavage of p130cas in etoposide-induced apoptotic Rat-1 cells. Kook, S., Shim, S.R., Choi, S.J., Ahnn, J., Kim, J.I., Eom, S.H., Jung, Y.K., Paik, S.G., Song, W.K. Mol. Biol. Cell (2000) [Pubmed]
  19. Reduction of tyrosine-phosphorylated proteins in involuted thymuses of stressed rats: a study using immunological methods. Nishio, H., Tsuji, H., Tamura, A., Suzuki, K. Electrophoresis (2000) [Pubmed]
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