PKC delta and zeta mediate IL-4/IL-13-induced germline epsilon transcription in human B cells: A putative regulation via PU.1 phosphorylation

We have investigated the role of PKC isozymes in the function of IL-4 and I L-13 in human B cells. In a Burkitt's B lymphoma cell line, DND39, IL-4 ind uced the translocation of PKC delta and zeta from the cytosol to the membra ne fraction. The activation of germline E promoter by IL-4 was abrogated no t only by the expression of dominant negative mutants of PKC delta and zeta but also by isozyme-selective PKC inhibitors, rottlerin and PKC zeta pseud osubstrate peptide. These inhibitors also suppressed IL-4/IL-13-induced ger mline epsilon transcription in the IL-13R alpha1-transfected DND39 cells as well as in normal human B cells, but had no influence on the induction of CD23b in the latter cells. As a downstream event of PKC, we found threonine phosphorylation of PU.1 in IL-4-stimulated DND39 cells. This phosphorylati on was suppressed by the PKC inhibitors, although STAT6 activation was unaf fected. These results suggest that, in human B cells, IL-4/IL-13 utilize PK C delta and zeta for the STAT6-independent signaling pathway and thereby mo dulate the transcriptional activity of PU.1. (C) 2001 Academic Press.