The protein-tyrosine kinase SYK interacts with TRAF-interacting protein TRIP in breast epithelial cells

摘要

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 plays a positive role in murine mammary tumor virus-mediated tumorigenesis. A yeast two-hybrid screen using a library from human mammary gland identified TRAF-interacting protein (TRIP) as a Syk-binding partner. This interaction is mediated by the C-terminal region of TRIP and is enhanced by the treatment of cells with tumor necrosis factor (TNF) and the tyrosine-phosphorylation of Syk. Syk and TRIP play opposing roles in TNF-signaling pathways. Syk enhances the activation of NF-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 co-expression of Syk.