PKCdelta 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 IL-13 in human B cells. In a Burkitt's B lymphoma cell line, DND39, IL-4 induced the translocation of PKCdelta and zeta from the cytosol to the membrane fraction. The activation of germline epsilon promoter by IL-4 was abrogated not only by the expression of dominant negative mutants of PKCdelta and zeta but also by isozyme-selective PKC inhibitors, rottlerin and PKCzeta pseudosubstrate peptide. These inhibitors also suppressed IL-4/IL-13-induced germline epsilon transcription in the IL-13Ralpha1-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 phosphorylation was suppressed by the PKC inhibitors, although STAT6 activation was unaffected. These results suggest that, in human B cells, IL-4/IL-13 utilize PKCdelta and zeta for the STAT6-independent signaling pathway and thereby modulate the transcriptional activity of PU.1.
Ikizawa
K
K
Clinical Research Center, National Sagamihara Hospital, Kanagawa 228-8522, Japan. k-ikizawa@taiho.co.jp
Kajiwara
K
K
Izuhara
K
K
Yanagihara
Y
Y
D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000235:genetics*; D018793:Interleukin-13 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology*; D007527:Isoenzymes / Q000502:physiology*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000502:physiology*; D051745:Protein Kinase C-delta; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D017455:Receptors, IgE / Q000096:biosynthesis / Q000235:genetics; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D000099232:Proto-Oncogene Protein Spi-1; D000099221:Protein Kinase C zeta
D004268:DNA-Binding Proteins; D007073:Immunoglobulin E; D018793:Interleukin-13; D015847:Interleukin-4; D007378:Interleukins; D007527:Isoenzymes; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D017455:Receptors, IgE; D015534:Trans-Activators; D014157:Transcription Factors; D000099232:Proto-Oncogene Protein Spi-1; D000099221:Protein Kinase C zeta; C497258:PRKCD protein, human