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Identification of STAT3 as a specific substrate of breast tumor kinase

Oncogene volume 25, pages 4904–4912 (2006)Cite this article

Abstract

Breast tumor kinase (Brk) is a non-receptor tyrosine kinase distantly related to the Src family kinase. It is expressed in more than 60% of breast tumors, but the biological role of this kinase remains to be determined. Only a limited number of substates have been identified for Brk, and the link of Brk to tumorigenesis remains largely unknown. In this study, we provide evidence that the signal transducer and activator of transcription 3, STAT3, is a physiological target of Brk. Activation of STAT3 previously has been linked to oncogenesis, and results in this study demonstrate that STAT3 is tyrosine phosphorylated and transcriptionally activated in cells expressing endogenous Brk. Signal transducer and activator of transcription 3 is specifically targeted since other STAT members are not responsive to Brk expression. Signal transducer and activator of transcription 3 activation requires the catalytic activity of Brk, and expression of both STAT3 and Brk stimulate cellular proliferation. In addition, we have identified a negative regulator of Brk, the suppressor of cytokine signaling, SOCS3. The SOCS3 protein is known to block signaling mediated by cytokine receptors, and here we find that SOCS3 is able to repress the activity of the Brk non-receptor tyrosine kinase.

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Acknowledgements

We thank all the members of the NCR laboratory, especially the assistance of Sarah Van Scoy. We thank our colleagues Dafna Bar-Sagi, Michael Hayman, and Patrick Hearing for their advice along the way. These studies were supported by NIH grants (RO1CA50773) (PPGCA28146), and in part by grants from the Carol Baldwin Breast Cancer Research Program to NCR, and the Italian Cancer Research Association to VP.

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Authors and Affiliations

  1. Department of Microbiology and Molecular Genetics, Stony Brook University, Stony Brook, NY, USA

    L Liu, Y Gao & N C Reich

  2. Department of Physiology and Biophysics, Stony Brook University, Stony Brook, NY, USA

    H Qiu & W T Miller

  3. Department of Genetics, Biology and Biochemistry, University of Turin, Turin, Italy

    V Poli

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Correspondence to N C Reich.

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Liu, L., Gao, Y., Qiu, H. et al. Identification of STAT3 as a specific substrate of breast tumor kinase. Oncogene 25, 4904–4912 (2006). https://doi.org/10.1038/sj.onc.1209501

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