Mechanisms of tumor necrosis factor action.
Tumor necrosis factor (TNF) is able to induce a great diversity of cellular responses via modulating the expression of a number of different genes. The multitude of TNF activities may be explained by both structural and functional heterogeneity in TNF receptors as well as by a diversification of postreceptor signal transduction pathways. Purification of TNF receptors has revealed two major, distinct binding proteins (TR60 and TR80). TR60 seems to be an essential component for TNF signaling; the functional role of TR80 remains to be elucidated. The pathway of postreceptor signal transduction involves phospholipase A2, a phosphatidylcholine-specific phospholipase C, protein kinase C, and other serine/threonine and tyrosine-specific protein kinases with as yet unknown function. At the receiving end of TNF signaling, induction of gene expression is mediated through activation of nuclear transcription factors, such as NFkB, AP-1, IRF-1, and NF-GMa.
Schütze
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Institut für Medizinische Mikrobiologie und Hygiene, Technische Universität München, Germany.
Machleidt
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Krönke
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D004075:Diglycerides / Q000096:biosynthesis; D004789:Enzyme Activation; D010741:Phospholipases A / Q000096:biosynthesis; D054467:Phospholipases A2; D011493:Protein Kinase C / Q000096:biosynthesis*; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor; D015398:Signal Transduction / Q000502:physiology*; D013379:Substrate Specificity; D014157:Transcription Factors / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D010738:Type C Phospholipases / Q000096:biosynthesis
D004075:Diglycerides; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D011493:Protein Kinase C; D010741:Phospholipases A; D054467:Phospholipases A2; D010738:Type C Phospholipases