IL-13 INDUCES TYROSINE PHOSPHORYLATION OF PHOSPHOLIPASE C-GAMMA-1 FOLLOWING IRS-2 ASSOCIATION IN HUMAN MONOCYTES - RELATIONSHIP WITH THE INHIBITORY EFFECT OF IL-13 ON ROI PRODUCTION

Here we analysed the involvement of tyrosine phosphorylation in the re gulation of the initial molecular events induced by IL-13 to modulate TPA-triggered reactive oxygen intermediates (ROI) production. Our data indicate that treatment of monocytes with a protein tyrosine kinase i nhibitor (herbimycin A) prevents IL-13-induced cAMP accumulation and s ubsequent ROI inhibition. We have previously demonstrated that cAMP ac cumulation dependes on inositol phosphates hydrolysis (InsP(s)) and in tracellular Ca2+ mobilisation. The inhibition of InsP(s) and intracell ular Ca2+ release by herbimycin A suggests a primary role of tyrosine kinases upstream PLC activation. We further specify that IL-13 stimula tes PLC-gamma 1 and IRS-2 tyrosine phosphorylation in human monocytes. We demonstrate for the first time that IL-13 induces the association of IRS-2 with PLC-gamma 1. We proposed here that PLC-gamma 1 is a new candidate recruited by IRS-2. (C) 1998 Academic Press.