Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi


  • Dominique M. Donato
  • Steven K. HanksEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_460


Historical Background

p130Cas is a major substrate of the  Src tyrosine kinase that functions in integrin signaling to promote cell motility, invasion, proliferation, and survival (reviewed by Defillipi et al. 2006; Tikhmyanova et al. 2010). p130Cas was first recognized in the late 1980s by immunoblot detection with an anti-phosphotyrosine antibody in cells transformed by retroviral oncogenes v- crk and v- src. The p130 designation indicates the apparent molecular mass of ∼130 kDa during SDS polyacrylamide gel electrophoresis (PAGE), and Cas is acronymic for “Crk-associated substrate.” Characterization of the direct interactions of p130Cas with the v-Crk and v-Src proteins was significant in the recognition of Src homology 2 (SH2) domains as phosphotyrosine-binding modules in signal transduction. p130Cas was independently identified as a...
This is a preview of subscription content, log in to check access.


  1. Brabek J, Constancio SS, Siesser PF, Shin NY, Pozzi A, Hanks SK. Crk-associated substrate tyrosine phosphorylation sites are critical for invasion and metastasis of SRC-transformed cells. Mol Cancer Res. 2005;3:307–15.CrossRefPubMedGoogle Scholar
  2. Chodniewicz D, Klemke RL. Regulation of integrin-mediated cellular responses through assembly of a CAS/Crk scaffold. Biochim Biophys Acta. 2004;1692:63–76.CrossRefPubMedGoogle Scholar
  3. Cowell LN, Graham JD, Bouton AH, Clarke CL, O’neill GM. Tamoxifen treatment promotes phosphorylation of the adhesion molecules, p130Cas/BCAR1, FAK and Src, via an adhesion-dependent pathway. Oncogene. 2006;25:7597–607.CrossRefPubMedGoogle Scholar
  4. Cunningham-Edmondson AC, Hanks SK. P130Cas substrate domain signaling promotes growth, migration, and invasion of estrogen-receptor-negative breast cancer cells. Breast Cancer Targets Ther. 2009;1:39–52.Google Scholar
  5. Defillipi P, Di Stefano P, Cabodi S. p130Cas: a versatile scaffold in signaling networks. Trends Cell Biol. 2006;16:257–63.CrossRefGoogle Scholar
  6. Donato DM, Ryzhova LM, Meenderink LM, Kaverina I, Hanks SK. Dynamics and mechanism of p130Cas localization to focal adhesions. J Biol Chem. 2010;285:20769–79.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Dorssers LC, van der Flier S, Brinkman A, van Agthoven T, Veldscholte J, Berns EM, et al. Tamoxifen resistance in breast cancer: elucidating mechanisms. Drugs. 2001;61:1721–33.CrossRefPubMedGoogle Scholar
  8. Honda H, Oda H, Nakamoto T, Honda Z, Sakai R, Suzuki T, et al. Cardiovascular anomaly, impaired actin bundling and resistance to Src-induced transformation in mice lacking p130Cas. Nat Genet. 1998;19:361–5.CrossRefPubMedGoogle Scholar
  9. Huang J, Sakai R, Furuichi T. The docking protein Cas links tyrosine phosphorylation signaling to elongation of cerebellar granule cell axons. Mol Biol Cell. 2006;17:3187–96.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Huang Z, Yazdani U, Thompson-Peer KL, Kolodkin AL, Terman JR. Crk-associated substrate (Cas) signaling protein functions with integrins to specify axon guidance during development. Development. 2007;134:2337–47.CrossRefPubMedGoogle Scholar
  11. Kovacic-Milivojević B, Roediger F, Almeida EA, Damsky CH, Gardner DG, Ilić D. Focal adhesion kinase and p130Cas mediate both sarcomeric organization and activation of genes associated with cardiac myocyte hypertrophy. Mol Biol Cell. 2001;12:2290–307.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Meenderink L, Ryzhova LM, Donato DM, Gochberg DF, Kaverina I, Hanks SK. P130Cas Src-binding and substrate domains have distinct roles in sustaining focal adhesion disassembly and promoting cell migration. PLoS ONE. 2010;5:e13412.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Polte TR, Hanks SK. Interaction between focal adhesion kinase and Crk-associated tyrosine kinase substrate p130Cas. Proc Natl Acad Sci U S A. 1995;92:10678–82.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Riggins RB, Thomas KS, Ta HQ, Wen J, Davis RJ, Schuh NR, et al. Physical and functional interactions between Cas and c-Src induce tamoxifen resistance of breast cancer cells through pathways involving epidermal growth factor receptor and signal transducer and activator of transcription 5b. Cancer Res. 2006;66:7007–15.CrossRefPubMedGoogle Scholar
  15. Rivera GM, Antoku S, Gelkop S, Shin NY, Hanks SK, Pawson T, et al. Requirement of Nck adaptors for actin dynamics and cell migration stimulated by platelet-derived growth factor B. Proc Natl Acad Sci U S A. 2006;103:9536–41.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Ruest PJ, Shin NY, Polte TR, Zhang X, Hanks SK. Mechanisms of CAS substrate domain tyrosine phosphorylation by FAK and Src. Mol Cell Biol. 2001;21:7641–52.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Sakai R, Iwamatsu A, Hirano N, Ogawa S, Tanaka T, Mano H, et al. A novel signaling molecule, p130, forms stable complexes in vivo with v-Crk and v-Src in a tyrosine phosphorylation-dependent manner. EMBO J. 1994;13:3748–56.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Sawada Y, Tamada M, Dubin-Thaler BJ, Cherniavskaya O, Sakai R, Tanaka S, et al. Force sensing by mechanical extension of the Src family kinase substrate p130Cas. Cell. 2006;127:1015–26.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Shin NY, Dise RS, Schneider-Mergener J, Ritchie MD, Kilkenny DM, Hanks SK. Subsets of the major tyrosine phosphorylation sites in Crk-associated substrate (CAS) are sufficient to promote cell migration. J Biol Chem. 2004;279:38331–7.CrossRefPubMedGoogle Scholar
  20. Tikhmyanova N, Little JL, Golemis EA. CAS proteins in normal and pathological cell growth control. Cell Mol Life Sci. 2010;67:1025–48.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Physics of Life Processes, Leiden Institute of PhysicsLeiden UniversityLeidenThe Netherlands
  2. 2.Department of Cell and Developmental BiologyVanderbilt University School of MedicineNashvilleUSA