INTERLEUKIN-4 (IL-4) INDUCES PHOSPHATIDYLINOSITOL 3-KINASE (P85) DEPHOSPHORYLATION - IMPLICATIONS FOR THE ROLE OF SHP-1 IN THE IL-4-INDUCEDSIGNALS IN HUMAN B-CELLS

Interleukin 4 (IL-4) is a potent cytokine produced by T cells and to a lesser extent by tumor-associated natural killer cells, basophils, an d mast cells, IL-4 treatment of T cells and macrophages leads to augme ntation of their cytotoxic activity, In human B cells, IL-4 is a poten t stimulator of Ig class switching from IgM to IgE, The diverse biolog ical responses induced by IL-4 are mediated through a high affinity re ceptor complex (IL-4R). Although a wealth of information has accumulat ed regarding IL-4R, the exact mechanisms of IL-4R-mediated signaling p athways in human B cells are not well defined, In an attempt to charac terize the IL-4-induced signals in human B cells, we have found that I L-4 treatment induced rapid dephosphorylation of the 85-kDa regulatory subunit of phosphatidylinositol 3-kinase. To identify the protein-tyr osine phosphatase involved in the IL-4-mediated dephosphorylation, we performed Western blot analysis using monoclonal antibodies specific t o protein-tyrosine phosphatases, Upon IL-4 treatment, SHP-1 was specif ically translocated to the cellular membrane fraction. Furthermore, im munoprecipitation studies revealed that SHP-1 could be specifically co immunoprecipitated with the IL-4R as well as with phosphatidylinositol 3-kinase (p85). Collectively, our observations suggest that in additi on to protein phosphorylation, protein tyrosine dephosphorylation may play a role in the IL-4-induced signaling pathways.