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Interaction between Brk kinase and insulin receptor substrate-4

Oncogene volume 24, pages 5656–5664 (2005)Cite this article

Abstract

Breast tumor kinase (Brk) is a member of the Frk family of nonreceptor tyrosine kinases that is overexpressed in a high percentage of human breast tumors. The downstream substrates and effectors of Brk remain largely unidentified. In this study, we carried out immunoprecipitation and mass spectrometry experiments to identify new Brk binding partners. One interacting protein was insulin receptor substrate 4 (IRS-4), a member of the IRS family. We confirmed that Brk associates with IRS-4 in resting and insulin-like growth factor 1 (IGF-1)-stimulated HEK 293 cells. The SH3 and SH2 domains of Brk are both involved in the association. The tyrosine phosphorylation of Brk increases after stimulation with IGF-1, and in MCF-7 breast cancer cells we show that the presence of IRS-4 enhances this effect. Finally, we demonstrate that endogenous Brk and IRS-4 interact in A431 human epidermoid carcinoma cells.

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Acknowledgements

This work was supported by a grant from the NIH to WTM (CA28146).

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Authors and Affiliations

  1. Department of Physiology and Biophysics, School of Medicine, State University of New York at Stony Brook, Stony Brook, 11794-8661, NY, USA

    Haoqun Qiu, Wenjuan Su & W Todd Miller

  2. Department of Computational, Proteomics and Biological Mass Spectrometry Laboratory, Analytical and Structural Sciences, GlaxoSmithKline Pharmaceuticals, King of Prussia, 19406, PA, USA

    Francesca Zappacosta & Roland S Annan

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Correspondence to W Todd Miller.

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Qiu, H., Zappacosta, F., Su, W. et al. Interaction between Brk kinase and insulin receptor substrate-4. Oncogene 24, 5656–5664 (2005). https://doi.org/10.1038/sj.onc.1208721

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