The protein-tyrosine kinase Syk interacts with TRAF-interacting protein TRIP in breast epithelial cells.
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-kappaB 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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Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907-2064, USA.
Geahlen
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D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D000072377:Syk Kinase; D047992:TNF Receptor-Associated Factor 2 / Q000502:physiology; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D020798:Two-Hybrid System Techniques
D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D047992:TNF Receptor-Associated Factor 2; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D014409:Tumor Necrosis Factor-alpha; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase