Abstract
The nonreceptor, protein-tyrosine kinase Syk is a suppressor of breast cancer progression whose expression is inversely correlated with the invasive behavior of cancer cells. In contrast, Syk has a positive function in murine mammary tumor virus-mediated tumorigenesis. A yeast two-hybrid screen using a library from human mammary gland identified tumor necrosis factor (TNF) receptor-associated factor-interacting protein (TRIP) as an Syk-binding partner. This interaction is mediated by the C-terminal region of TRIP and is enhanced by the treatment of cells with TNF and the tyrosine phosphorylation of Syk. Syk and TRIP have opposing functions in TNF-signaling pathways. Syk enhances the activation of nuclear factor-κB by TNF and this is antagonized by TRIP. The overexpression of TRIP sensitizes cells to TNF-induced apoptosis, an effect that can be reversed by the coexpression of Syk.
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Acknowledgements
This work was supported by United States Public Health Services grant CA115465 awarded by the National Cancer Institute and US Army Breast Cancer Research Program award DAMD17-02-1-0554.
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Zhou, Q., Geahlen, R. The protein-tyrosine kinase Syk interacts with TRAF-interacting protein TRIP in breast epithelial cells. Oncogene 28, 1348–1356 (2009). https://doi.org/10.1038/onc.2008.493
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DOI: https://doi.org/10.1038/onc.2008.493
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