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.
Similar content being viewed by others
References
Besse A, Campos AD, Webster WK, Darnay BG . (2007). TRAF-interacting protein (TRIP) is a RING-dependent ubiquitin ligase. Biochem Biophys Res Commun 359: 660–664.
Coopman PJ, Do MT, Barth M, Bowden ET, Hayes AJ, Basyuk E et al. (2000). The Syk tyrosine kinase suppresses malignant growth of human breast cancer cells. Nature 406: 742–747.
Eliopoulos AG, Das S, Tsichlis PN . (2006). The tyrosine kinase Syk regulates TPL2 activation signals. J Biol Chem 281: 1371–1380.
Katz E, Lareef MH, Rassa JC, Grande SM, King LB, Russo J et al. (2005). MMTV Env encodes an ITAM responsible for transformation of mammary epithelial cells in three-dimensional culture. J Exp Med 201: 431–439.
Keshvara LM, Isaacson CC, Yankee TM, Sarac R, Harrison ML, Geahlen RL . (1998). Syk- and Lyn-dependent phosphorylation of Syk on multiple tyrosines following B cell activation includes a site that negatively regulates signaling. J Immunol 161: 5276–5283.
Kurosaki T . (2000). Functional dissection of BCR signaling pathways. Curr Opin Immunol 12: 276–281.
Latour S, Veillette A . (2001). Proximal protein tyrosine kinases in immunoreceptor signaling. Curr Opin Immunol 13: 299–306.
Lee SY, Lee SY, Choi Y . (1997). TRAF-interacting protein (TRIP): a novel component of the tumor necrosis factor receptor (TNFR)- and CD30-TRAF signaling complexes that inhibits TRAF2-mediated NF-kappaB activation. J Exp Med 185: 1275–1285.
Lu J, Lin W-H, Chen S-Y, Longnecker R, Tsai S-C, Chen C-L et al. (2006). Syk tyrosine kinase mediates Epstein-Barr virus latent membrane protein 2A-induced cell migration in epithelial cells. J Biol Chem 281: 8806–8814.
Ma H, Yankee TM, Hu J, Asai DJ, Harrison ML, Geahlen RL . (2001). Visualization of Syk-antigen receptor interactions using green fluorescent protein: differential roles for Syk and Lyn in the regulation of receptor capping and internalization. J Immunol 166: 1507–1516.
Moon KD, Post CB, Durden DL, Zhou Q, De P, Harrison ML et al. (2004). Molecular basis for a direct interaction between the Syk protein-tyrosine kinase and phosphoinositide 3-kinase. J Biol Chem 280: 1543–1551.
Moroni M, Soldatenkov V, Zhang L, Zhang Y, Stoica G, Gehan E et al. (2004). Progressive loss of Syk and abnormal proliferation in breast cancer cells. Cancer Res 64: 7346–7354.
Peters JD, Furlong MT, Asai DJ, Harrison ML, Geahlen RL . (1996). Syk, activated by cross-linking the B-cell antigen receptor, localizes to the cytosol where it interacts with and phosphorylates alpha-tubulin on tyrosine. J Biol Chem 271: 4755–4762.
Regamey A, Hohl D, Liu JW, Roger T, Kogerman P, Toftgard R et al. (2003). The tumor suppressor CYLD interacts with TRIP and regulates negatively nuclear factor kappaB activation by tumor necrosis factor. J Exp Med 198: 1959–1964.
Salomoni P, Khelifi AF . (2006). Daxx: death or survival protein? Trends Cell Biol 16: 97–104.
Takada Y, Aggarwal BB . (2004). TNF activates Syk protein tyrosine kinase leading to TNF-induced MAPK activation, NF-kappaB activation, and apoptosis. J Immunol 173: 1066–1077.
Toyama T, Iwase H, Yamashita H, Hara Y, Omoto Y, Sugiura H et al. (2003). Reduced expression of the Syk gene is correlated with poor prognosis in human breast cancer. Cancer Lett 189: 97–102.
Ulanova M, Puttagunta L, Marcet-Palacios M, Duszyk M, Steinhoff U, Duta F et al. (2005). Syk tyrosine kinase participates in beta1-integrin signaling and inflammatory responses in airway epithelial cells. Am J Physiol Lung Cell Mol Physiol 288: L497–L507.
Wang L, Devarajan E, He J, Reddy SP, Dai JL . (2005). Transcription repressor activity of spleen tyrosine kinase mediates breast tumor suppression. Cancer Res 65: 10289–10297.
Wilson J, Balkwill F . (2002). The role of cytokines in the epithelial cancer microenvironment. Semin Cancer Biol 12: 113–120.
Zhou F, Hu J, Ma H, Harrison ML, Geahlen RL . (2006). Nucleocytoplasmic trafficking of the Syk protein-tyrosine kinase. Mol Cell Biol 26: 3478–3491.
Zyss D, Montcourrier P, Vidal B, Anguille C, Mérezègue F, Sahuquet A et al. (2005). The Syk tyrosine kinase localizes to the centrosomes and negatively affects mitotic progression. Cancer Res 65: 10872–10880.
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.
Author information
Authors and Affiliations
Corresponding author
Additional information
Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)
Supplementary information
Rights and permissions
About this article
Cite this article
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
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/onc.2008.493
- Springer Nature Limited
Keywords
This article is cited by
-
TRAIP modulates the IGFBP3/AKT pathway to enhance the invasion and proliferation of osteosarcoma by promoting KANK1 degradation
Cell Death & Disease (2021)
-
TRAIP is involved in chromosome alignment and SAC regulation in mouse oocyte meiosis
Scientific Reports (2016)
-
TRAIP regulates replication fork recovery and progression via PCNA
Cell Discovery (2016)
-
NOPO modulates Egr-induced JNK-independent cell death in Drosophila
Cell Research (2012)
-
The TRAF-Interacting Protein (TRIP) Is a Regulator of Keratinocyte Proliferation
Journal of Investigative Dermatology (2011)