Signal transduction by the IL-1 type I receptor: evidence for the involvement of a receptor-coupled protein kinase.
A novel serine/threonine specific protein kinase was found to be associated with the type I IL-1 receptor in the murine T cell lines D10N and EL-4. This kinase was identified in immunoprecipitates from IL-1 stimulated T-cells by its ability to phosphorylate exogenous substrates in the presence of radiolabeled ATP. An endogenous protein, most likely a member of the IL-1 R1 complex, was also phosphorylated. The activation of the kinase is specific for IL-1, neither TNF nor phorbol esters were able to activate the IL-1 RI associated kinase activity. The IL-1 receptor antagonist had no intrinsic activity and inhibited the activation of the kinase. The activation of the kinase was rapid and detectable after 30 seconds of IL-1 stimulation. A minimal model of the IL-RI signal transduction complex is discussed, presenting this novel serine/threonine kinase as a constituent of the complex.
Martin
M
M
Institut für Molekularpharmakologie, Medizinische Hochschule Hannover, Germany.
Brigelius-Flohé
R
R
Resch
K
K
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008961:Models, Structural; D011487:Protein Conformation; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017472:Receptors, Interleukin-1 / Q000737:chemistry* / Q000502:physiology*; D012795:Sialoglycoproteins / Q000378:metabolism; D015398:Signal Transduction; D019311:Staurosporine; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000470:Alkaloids; D004791:Enzyme Inhibitors; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D047428:Protein Kinase Inhibitors; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D019311:Staurosporine