PMID:19151749

Citation	Zhou, Q and Geahlen, RL (2009) The protein-tyrosine kinase Syk interacts with TRAF-interacting protein TRIP in breast epithelial cells. Oncogene 28:1348-56
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-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.
Links	PubMed PMC2656405 Online version:10.1038/onc.2008.493
Keywords	Breast Neoplasms/metabolism; Breast Neoplasms/pathology; Cell Line, Tumor; Female; Humans; Immunoprecipitation; Intracellular Signaling Peptides and Proteins/physiology; NF-kappa B/metabolism; Phosphorylation; Protein-Tyrosine Kinases/physiology; TNF Receptor-Associated Factor 2/physiology; Tumor Necrosis Factor Receptor-Associated Peptides and Proteins/physiology; Tumor Necrosis Factor-alpha/pharmacology; Two-Hybrid System Techniques
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:KSYK	involved_in	GO:0010803: regulation of tumor necrosis factor-mediated signaling pathway	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:KSYK		GO:1901224: positive regulation of NIK/NF-kappaB cascade	ECO:0000314:		P		Fig 1.B Increased TNF signaling by Syk here demonstrates increased NF-kB activation.	complete CACAO 8563
HUMAN:KSYK		GO:0006468: protein phosphorylation	ECO:0000315:		P		1.B Syk phosphorylates TRIP.	complete CACAO 8564
HUMAN:KSYK		GO:0006468: protein phosphorylation	ECO:0000314:		P		Fig 1.C Syk phosphorylated TRIP.	complete CACAO 8565
HUMAN:KSYK	Colocalizes with	GO:0005737: cytoplasm	ECO:0000314:		C		Figure 4c and D show that when SKY and TRIAP in Human breast cells MCF7 cells are coexpressed then both are found in the cytoplasm. This is not normal for SKY which is normally found throughout the cell.	complete CACAO 9148
HUMAN:KSYK		GO:0010803: regulation of tumor necrosis factor-mediated signaling pathway	ECO:0000315:		P		SKY expression led to increased activity of the the TNF signaling pathway of resulting in activation of NF-kB as shown in Figure 5 particularly in C and D. Thus sky positively regulates TNF mediated signaling pathway.	complete CACAO 9160
HUMAN:TRAIP	involved_in	GO:0010804: negative regulation of tumor necrosis factor-mediated signaling pathway	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:TRAIP		GO:0034504: protein localization to nucleus	ECO:0000314:		P		figure 4A shows Trip colocalized into the nucleoli of the nucleus via immunoflorescence of MCF7 cells with overexpressed TRIP.	complete CACAO 9134
HUMAN:TRAIP		GO:0034504: protein localization to nucleus	ECO:0000315:		P		Trip knockdown with siRNA in figure 4B leads to reduced TRIP in the nucleoli of the nucleus in MCF7 cells showing that when trip is being expressed it is localized in the nucleoli of the nucleus.	complete CACAO 9135
HUMAN:TRAIP	Colocalizes with	GO:0005737: cytoplasm	ECO:0000314:		C		Figure 4c and D shows when Sky-EGFP and TRIP were coexpressed then TRIP is colocalized along with SKY in the cytoplasm.	complete CACAO 9139
HUMAN:TRAIP		GO:0010804: negative regulation of tumor necrosis factor-mediated signaling pathway	ECO:0000314:		P		Increasing amounts of TRIP results in decreased activation of NF-kB by the TNF mediated pathway. This is indicated in Figure 6 and Supplemental figure 3.	complete CACAO 9167

References

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