Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

c-Src Family of Tyrosine Kinases

  • Banibrata SenEmail author
  • Faye M. Johnson
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_54


 ASV;  c-SRC;  p60-Src;  SRC;  SRC1

Historical Background

In 1911, pathologist Francis Peyton Rous isolated a virus from a Plymouth Rock chicken that has continued to bear his name, the Rous sarcoma virus (RSV) (Rous 1911). Rous sarcoma virus is the archetypal retrovirus, capable of causing tumors in chickens and rapidly transforming cells in culture with high efficiency through production of the protein viral sarcoma (v-Src), the first identified transforming protein. In 1976, Bishop and Varmus demonstrated that the v-Src gene has a normal cellular homolog gene (protooncogene), c-Src, and that the v-Src gene product, pp60v-Src or v-Src, is a phosphoprotein with an apparent molecular mass of 60 kDa with intrinsic protein kinase activity (Stehelin et al. 1976). Sequencing of the chicken c-Src gene and the RSV v-Src gene demonstrated that the two genes are closely related except at the C-terminal end, and it is this structural difference that leads to constitutive activation of v-Src...

This is a preview of subscription content, log in to check access.


  1. Bjorge JD, Pang A, Fujita DJ. Identification of protein-tyrosine phosphatase 1B as the major tyrosine phosphatase activity capable of dephosphorylating and activating c-Src in several human breast cancer cell lines. J Biol Chem. 2000;275(52):41439–46.PubMedCrossRefGoogle Scholar
  2. Brooks HD, Glisson BS, Bekele BN, Johnson FM, Ginsberg LE, El-Naggar A, Culotta KS, Takebe N, Wright J, Tran HT, Papadimitrakopoulou VA. Phase 2 study of dasatinib in the treatment of head and neck squamous cell carcinoma. Cancer. 2011;117(10):2112–9.PubMedCrossRefGoogle Scholar
  3. Byers LA, Sen B, Saigal B, Diao L, Wang J, Nanjundan M, Cascone T, Mills GB, Heymach JV, Johnson FM. Reciprocal regulation of c-Src and STAT3 in non-small cell lung cancer. Clin Cancer Res. 2009;15(22):6852–61.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Frame MC. Src in cancer: deregulation and consequences for cell behaviour. Biochim Biophys Acta. 2002;1602(2):114–30.PubMedPubMedCentralGoogle Scholar
  5. Haura EB, Tanvetyanon T, Chiappori A, Williams C, Simon G, Antonia S, Gray J, Litschauer S, Tetteh L, Neuger A, Song L, Rawal B, Schell MJ, Bepler G. Phase I/II study of the Src inhibitor dasatinib in combination with erlotinib in advanced non-small-cell lung cancer. J Clin Oncol. 2010;28(8):1387–94.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Irby RB, Mao W, Coppola D, Kang J, Loubeau JM, Trudeau W, Karl R, Fujita DJ, Jove R, Yeatman TJ. Activating SRC mutation in a subset of advanced human colon cancers. Nat Genet. 1999;21(2):187–90.PubMedCrossRefGoogle Scholar
  7. Johnson FM, Gallick GE. SRC family nonreceptor tyrosine kinases as molecular targets for cancer therapy. Anti Cancer Agents Med Chem. 2007;7(6):651–9.CrossRefGoogle Scholar
  8. Johnson FM, Gallick GE. Src family kinase inhibitors in cancer therapy. In: Georgiev B, Markovski S, editors. Serpins and protein kinase inhibitors: novel functions, structural features and molecular mechanisms. 6 New York: Nova Science; 2010. p. 125–53.Google Scholar
  9. Johnson FM, Saigal B, Talpaz M, Donato NJ. Dasatinib (BMS-354825) tyrosine kinase inhibitor suppresses invasion and induces cell cycle arrest and apoptosis of head and neck squamous cell carcinoma and non-small cell lung cancer cells. Clin Cancer Res. 2005;11(19 Pt 1):6924–32.PubMedCrossRefGoogle Scholar
  10. Johnson FM, Bekele BN, Feng L, Wistuba I, Tang XM, Tran HT, Erasmus JJ, Hwang LL, Takebe N, Blumenschein GR, Lippman SM, Stewart DJ. Phase II study of dasatinib in patients with advanced non-small-cell lung cancer. J Clin Oncol. 2010;28(30):4609–15.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Kelley LC, Ammer AG, Hayes KE, Martin KH, Machida K, Jia L, Mayer BJ, Weed SA. Oncogenic Src requires a wild-type counterpart to regulate invadopodia maturation. J Cell Sci. 2010;123(Pt 22):3923–32.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Lehrer S, O’Shaughnessy J, Song HK, Levine E, Savoretti P, Dalton J, Lipsztein R, Kalnicki S, Bloomer WD. Activity of pp 60c-src protein kinase in human breast cancer. Mt Sinai J Med. 1989;56(2):83–5.PubMedPubMedCentralGoogle Scholar
  13. Leung EL, Wong JC, Johlfs MG, Tsang BK, Fiscus RR. Protein kinase G type Ialpha activity in human ovarian cancer cells significantly contributes to enhanced Src activation and DNA synthesis/cell proliferation. Mol Cancer Res. 2010;8(4):578–91.PubMedCrossRefGoogle Scholar
  14. Okamoto W, Okamoto I, Yoshida T, Okamoto K, Takezawa K, Hatashita E, Yamada Y, Kuwata K, Arao T, Yanagihara K, Fukuoka M, Nishio K, Nakagawa K. Identification of c-Src as a potential therapeutic target for gastric cancer and of MET activation as a cause of resistance to c-Src inhibition. Mol Cancer Ther. 2010;9(5):1188–97.PubMedCrossRefGoogle Scholar
  15. Rothschild SI, Gautschi O, Haura EB, Johnson FM. Src inhibitors in lung cancer: current status and future directions. Clin Lung Cancer. 2010;11(4):238–42.PubMedCrossRefGoogle Scholar
  16. Rous P. A sarcoma of the fowl transmissible by an agent separable from the tumor cells. J Exp Med. 1911;13(4):397–411.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Sen B, Johnson FM. Regulation of Src family kinases in human cancers. J Signal Transduct. 2011;1–14.CrossRefGoogle Scholar
  18. Sen B, Saigal B, Parikh N, Gallick G, Johnson FM. Sustained Src inhibition results in signal transducer and activator of transcription 3 (STAT3) activation and cancer cell survival via altered Janus-activated kinase-STAT3 binding. Cancer Res. 2009;69(5):1958–65.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Sen B, Peng S, Saigal B, Williams MD, Johnson FM. Distinct interactions between c-Src and c-Met in mediating resistance to c-Src inhibition in head and neck cancer. Clin Cancer Res. 2011;17(3):514–24.PubMedCrossRefGoogle Scholar
  20. Stehelin D, Varmus HE, Bishop JM, Vogt PK. DNA related to the transforming gene(s) of avian sarcoma viruses is present in normal avian DNA. Nature. 1976;260(5547):170–3.PubMedCrossRefGoogle Scholar
  21. Summy JM, Gallick GE. Src family kinases in tumor progression and metastasis. Cancer Metastasis Rev. 2003;22(4):337–58.PubMedCrossRefGoogle Scholar
  22. Takeya T, Hanafusa H. Structure and sequence of the cellular gene homologous to the RSV src gene and the mechanism for generating the transforming virus. Cell. 1983;32(3):881–90.PubMedCrossRefGoogle Scholar
  23. Thomas S, Overdevest JB, Nitz MD, Williams PD, Owens CR, Sanchez-Carbayo M, Frierson HF, Schwartz MA, Theodorescu D. Src and caveolin-1 reciprocally regulate metastasis via a common downstream signaling pathway in bladder cancer. Cancer Res. 2011;71(3):832–41.PubMedCrossRefGoogle Scholar
  24. Zhang XH, Wang Q, Gerald W, Hudis CA, Norton L, Smid M, Foekens JA, Massague J. Latent bone metastasis in breast cancer tied to Src-dependent survival signals. Cancer Cell. 2009;16(1):67–78.PubMedPubMedCentralCrossRefGoogle Scholar
  25. Zheng XM, Wang Y, Pallen CJ. Cell transformation and activation of pp 60c-Src by overexpression of a protein tyrosine phosphatase. Nature. 1992;359(6393):336–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of Thoracic/Head and Neck Medical Oncology, Unit 432The University of Texas MD Anderson Cancer CenterHoustonUSA
  2. 2.The University of Texas Graduate School of Biomedical Sciences at HoustonHoustonUSA