INTERLEUKIN-1-INDUCED ACTIVATION OF A PROTEIN-KINASE CO-PRECIPITATINGWITH THE TYPE-I INTERLEUKIN-1 RECEPTOR IN T-CELLS

We have investigated the possibility of a protein kinase participating in the signal transduction mechanisms of the interleukin-1 (IL-1) typ e I receptor (IL-1RI). Our data show that a protein kinase was co-prec ipitated with the IL-1 RI from the two murine T helper cell lines D 10 N and EL-4. The kinase activity was detected in an in vitro kinase ass ay performed with the immune beads in the presence of exogenous substr ates. IL-1 treatment of the cells resulted in a rapid activation of th is protein kinase in a concentration-dependent manner. Both forms of I L-1, IL-1 alpha and IL-1 beta, induced this kinase activity, whereas t he IL-1 receptor antagonist (IL-1ra) was inactive. In excess IL-1ra co mpetitively antagonized IL-1 stimulation. In the in vitro kinase assay the exogenous substrates myelin basic protein and histone H-1 were ph osphorylated, whereas casein or heat-shock protein HSP27 were not acce pted, reflecting a certain selectivity of this protein kinase. The IL- 1RI co-precipitable protein kinase showed a serine/threonine specifici ty and was inhibited by staurosporine, but not by inhibitors specific for protein tyrosine kinases or protein kinase C. These results show t hat a serine/threonine protein kinase directly interacts with the IL-1 RI at the plasma membrane level of T helper cells forming a novel type of IL-1 inducible signaling complex. This protein kinase may resemble the link coupling the plasma membrane IL-1 receptor to cytosolic down stream elements in the IL-1 signaling pathway.