title: Tumor necrosis factor stimulates multiple serine/threonine protein kinases in Swiss 3T3 and L929 cells. Implication of casein kinase-2 and extracellular signal-regulated kinases in the tumor necrosis factor signal transduction pathway.
abstract: Incubation of Swiss 3T3 or L929 cells with tumor necrosis factor (TNF) leads to the rapid stimulation of several cytosolic Ser/Thr kinases active toward myelin basic protein, the S6 peptide (RRLSSLR), the G peptide (SPQPSRRGSESSEE), and Kemptide (LRRASLG). This confirms the hypothesis that kinases other than protein kinases A and C may be involved in the TNF signal transduction. Chromatography on Mono Q resolved multiple kinase peaks with each substrate tested and moreover revealed a TNF-mediated casein kinase-2 activation in both cell lines, measurable with the specific RRREEESEEE peptide or with the G peptide. The TNF-stimulated myelin basic protein kinases-1 and -2 were identified as extracellular signal-regulated kinases-2 and -1, respectively, based on their elution pattern on Mono Q chromatography, their inactivation by protein phosphatase action, their reaction with phosphothreonine and phosphotyrosine antibodies, and by their migration on sodium dodecyl sulfate-polyacrylamide gel electrophoresis as 42- and 44-kDa proteins recognized by anti-extracellular signal-regulated kinase antibodies.
mesh_terms: D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D047388:Casein Kinases; D002852:Chromatography, Ion Exchange; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000378:metabolism; D007700:Kinetics; D007739:L Cells; D051379:Mice; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000378:metabolism; D009842:Oligopeptides / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D011494:Protein Kinases / Q000302:isolation & purification / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013379:Substrate Specificity; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D004676:Myelin Basic Protein; D009842:Oligopeptides; D014409:Tumor Necrosis Factor-alpha; C037642:kemptide; D011494:Protein Kinases; D047388:Casein Kinases; D010749:Phosphoprotein Phosphatases; D019204:GTP-Binding Proteins