Tumor necrosis factor (TNF) is a major mediator of apoptosis as well a! inflammation and immunity, and it has been implicated in the pathogenesis of a wide spectrum of human diseases, including sepsis, diabetes, cancer osteoporosis, multiple sclerosis, rheumatoid arthritis, and inflammatory bowel diseases. The interaction of TNF with TNF receptor-1 (TNF-R1) activated several signal transduction pathways. A common feature of each pathway h the TNF-induced formation of a multiprotein signaling complex at the cell membrane. Over the past decade, many of the components and mechanisms of these signaling pathways have been elucidated. We provide an overview of current knowledge of TNF signaling and introduce an STKE Connections Map that depicts a canonical view of this process.
