Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Csk-binding protein (Cbp) negatively regulates epidermal growth factor-induced cell transformation by controlling Src activation

Oncogene volume 25, pages 5495–5506 (2006)Cite this article

Abstract

Epidermal growth factor receptor (EGFR) and Src tyrosine kinase cooperate in regulating EGFR-mediated cell signaling and promoting cell transformation and tumorigenesis in pathological conditions. Activation of Src is tightly regulated by the C-terminal Src kinase (Csk). The Csk-binding protein (Cbp) is a ubiquitously expressed transmembrane protein. Its functions include suppression of T-cell receptor activation through recruiting Csk and inhibiting Src family kinase (SFK). However, a potential role of Cbp in EGF-induced cell activities has not been investigated. Here, we report that EGF-stimulation-induced Cbp tyrosine phosphorylation followed by Cbp–Csk association, in a SFK-dependent manner. Expression of wild-type (wt) Cbp remarkably suppressed EGF-induced activation of Src, ERK1/2, and Akt-1 enzymes, and NIH3T3 cell transformation, as well as colony formation of a breast cancer cell line (MDA-MB-468) in soft agar. In contrast, expression of CbpY317F or knockdown endogenous Cbp in NIH3T3 cells by RNA interference significantly enhanced EGF-induced activation of these enzymes and cell transformation. In addition, overexpression of multiple receptor tyrosine kinases (RTKs)-induced Cbp tyrosine phosphorylation. These results demonstrate that Cbp functions as a negative regulator of cell transformation and tumor cell growth through downregulation of Src activation, suggesting that Cbp might be broadly involved in RTKs-activated signaling pathways and tumorigenesis.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
Figure 10

Similar content being viewed by others

References

  • Baumeister U, Funke R, Ebnet K, Vorschmitt H, Koch S, Vestweber D . (2005). EMBO J 24: 1686–1695.

  • Baumgartner M, Angelisova P, Setterblad N, Mooney N, Werling D, Horejsi V et al. (2003). Blood 101: 1874–1881.

  • Biscardi JS, Belsches AP, Parsons SJ . (1998). Mol Carcinog 21: 261–272.

  • Biscardi JS, Maa MC, Tice DA, Cox ME, Leu TH, Parsons SJ . (1999). J Biol Chem 274: 8335–8343.

  • Bivona TG, Perez De Castro I, Ahearn IM, Grana TM, Chiu VK, Lockyer PJ et al. (2003). Nature 424: 694–698.

  • Brdicka T, Pavlistova D, Leo A, Bruyns E, Korinek V, Angelisova P et al. (2000). J Exp Med 191: 1591–1604.

  • Cance WG, Liu ET . (1995). Breast Cancer Res Treat 35: 105–114.

  • Cao H, Sanguinetti AR, Mastick CC . (2004). Exp Cell Res 294: 159–171.

  • Couet J, Li S, Okamoto T, Ikezu T, Lisanti MP . (1997). J Biol Chem 272: 6525–6533.

  • Davidson D, Bakinowski M, Thomas ML, Horejsi V, Veillette A . (2003). Mol Cell Biol 23: 2017–2028.

  • DeMali KA, Godwin SL, Soltoff SP, Kazlauskas A . (1999). Exp Cell Res 253: 271–279.

  • Di Fiore PP, Pierce JH, Fleming TP, Hazan R, Ullrich A, King CR et al. (1987). Cell 51: 1063–1070.

  • Dobenecker MW, Schmedt C, Okada M, Tarakhovsky A . (2005). Mol Cell Biol 25: 10533–10542.

  • Franke TF, Hornik CP, Segev L, Shostak GA, Sugimoto C . (2003). Oncogene 22: 8983–8998.

  • Ishizawar R, Parsons SJ . (2004). Cancer Cell 6: 209–214.

  • Ishizawar RC, Tice DA, Karaoli T, Parsons SJ . (2004). J Biol Chem 279: 23773–23781.

  • Jiang T, Qiu Y . (2003). J Biol Chem 278: 15789–15793.

  • Karni R, Jove R, Levitzki A . (1999). Oncogene 18: 4654–4662.

  • Kassenbrock CK, Hunter S, Garl P, Johnson GL, Anderson SM . (2002). J Biol Chem 277: 24967–24975.

  • Kawabuchi M, Satomi Y, Takao T, Shimonishi Y, Nada S, Nagai K et al. (2000). Nature 404: 999–1003.

  • Kharitonenkov A, Chen Z, Sures I, Wang H, Schilling J, Ullrich A . (1997). Nature 386: 181–186.

  • Kim YN, Dam P, Bertics PJ . (2002). Exp Cell Res 280: 134–147.

  • Kong M, Mounier C, Dumas V, Posner BI . (2003). J Biol Chem 278: 5837–5844.

  • Lev DC, Kim LS, Melnikova V, Ruiz M, Ananthaswamy HN, Price JE . (2004). Br J Cancer 91: 795–802.

  • Lisanti MP, Scherer PE, Vidugiriene J, Tang Z, Hermanowski-Vosatka A, Tu YH et al. (1994). J Cell Biol 126: 111–126.

  • Lu Y, Yu Q, Liu JH, Zhang J, Wang H, Koul D et al. (2003). J Biol Chem 278: 40057–40066.

  • Maa MC, Leu TH, McCarley DJ, Schatzman RC, Parsons SJ . (1995). Proc Natl Acad Sci USA 92: 6981–6985.

  • Mason CS, Springer CJ, Cooper RG, Superti-Furga G, Marshall CJ, Marais R . (1999). EMBO J 18: 2137–2148.

  • Matsuoka H, Nada S, Okada M . (2004). J Biol Chem 279: 5975–5983.

  • Nguyen DM, Schrump DS . (2004). Semin Thorac Cardiovasc Surg 16: 3–12.

  • Ohtake H, Ichikawa N, Okada M, Yamashita T . (2002). J Immunol 168: 2087–2090.

  • Okamoto T, Schlegel A, Scherer PE, Lisanti MP . (1998). J Biol Chem 273: 5419–5422.

  • Olayioye MA, Beuvink I, Horsch K, Daly JM, Hynes NE . (1999). J Biol Chem 274: 17209–17218.

  • Rae JM, Lippman ME . (2004). Breast Cancer Res Treat 83: 99–107.

  • Roche S, Koegl M, Barone MV, Roussel MF, Courtneidge SA . (1995). Mol Cell Biol 15: 1102–1109.

  • Shien T, Doihara H, Hara H, Takahashi H, Yoshitomi S, Taira N et al. (2004). Breast Cancer 11: 367–373.

  • Shima T, Nada S, Okada M . (2003). Proc Natl Acad Sci USA 100: 14897–14902.

  • Simons K, Ikonen E . (1997). Nature 387: 569–572.

  • Smart EJ, Ying YS, Mineo C, Anderson RG . (1995). Proc Natl Acad Sci USA 92: 10104–10108.

  • Song KS, Li S, Okamoto T, Quilliam LA, Sargiacomo M, Lisanti MP . (1996). J Biol Chem 271: 9690–9697.

  • Tremblay L, Hauck W, Aprikian AG, Begin LR, Chapdelaine A, Chevalier S . (1996). Int J Cancer 68: 164–171.

  • Tsuruda A, Suzuki S, Maekawa T, Oka S . (2004). FEBS Lett 560: 215–220.

  • Van Slyke P, Coll ML, Master Z, Kim H, Filmus J, Dumont DJ . (2005). Mol Cell Biol 25: 3831–3841.

  • Wang B, Lemay S, Tsai S, Veillette A . (2001). Mol Cell Biol 21: 1077–1088.

  • Wilson LK, Luttrell DK, Parsons JT, Parsons SJ . (1989). Mol Cell Biol 9: 1536–1544.

  • Xu S, Huo J, Tan JE, Lam KP . (2005). Mol Cell Biol 25: 8486–8495.

  • Yarden Y, Sliwkowski MX . (2001). Nat Rev Mol Cell Biol 2: 127–137.

  • Yayon A, Ma YS, Safran M, Klagsbrun M, Halaban R . (1997). Oncogene 14: 2999–3009.

  • Zhang SQ, Yang W, Kontaridis MI, Bivona TG, Wen G, Araki T et al. (2004). Mol Cell 13: 341–355.

Download references

Acknowledgements

We thank Dr Axel Ullrich for providing the plasmids and cell lines as mentioned in Materials and methods. This work was supported by the grants from National Natural Science Foundation of China (No. 30270335) and from the Ministry of Science and Technology, China (No. 2001AA233031 and No. 2001CB510205) and also from Shanghai-Anson Research Foundation (SHARF).

Author information

Authors and Affiliations

  1. Key Laboratory of Proteomics, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China

    L Q Jiang, X Feng, W Zhou & Z Chen

  2. SHARF Laboratory, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China

    Z Chen

  3. Graduate School of the Chinese Academy of Sciences, Max-Planck-Institute of Biochemistry, Martinsried, Germany

    L Q Jiang, X Feng & W Zhou

  4. Department of Molecular Biology, Max-Planck-Institute of Biochemistry, Martinsried, Germany

    P G Knyazev & A Ullrich

Authors
  1. L Q Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. X Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. W Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P G Knyazev
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A Ullrich
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Z Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Z Chen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jiang, L., Feng, X., Zhou, W. et al. Csk-binding protein (Cbp) negatively regulates epidermal growth factor-induced cell transformation by controlling Src activation. Oncogene 25, 5495–5506 (2006). https://doi.org/10.1038/sj.onc.1209554

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1209554

Keywords

This article is cited by

Search

Advanced search

Quick links