INTERLEUKIN-13 INDUCES RAPID TYROSINE PHOSPHORYLATION AND ACTIVATION OF RAF-1 KINASE IN HUMAN MONOCYTIC PROGENITOR-CELL LINE U937

IL-13 is a pleiotropic cytokine produced by Th0, Th1-like, and CD8 T c ells in response to antigen stimulation. Its biological effects includ e suppression of cytotoxic activity of monocytes/macrophages and suppr ession of pro-inflamatory cytokine production. However, the mechanism of IL-13 remains unknown. In this study we investigated the effects of rhIL-13 on tyrosine phosphorylation in U937 monocytic progenitor cell s by immunoblotting and immunocomplex kinase assays. We demonstrate th at rhIL-13 stimulates dose-dependent tyrosine phosphorylation of sever al proteins of Mr. 93, 80, 74, 49.5, 42, 30, 22 and 18 kDa within 30 s ec. The effect of IL-13 was blocked by the tyrosine kinase inhibitor e rbstatin. Furthermore, IL-13 induces tyrosine phosphorylation and rapi d activation of raf-1 kinase. These findings provide the first evidenc e that the mechanism of IL-13 involves rapid tryrosine phosphorylation and activation of raf-1 serine/threonine kinase. (C) 1995 Academic Pr ess, Inc.