Jain N, Zhang T, Kee WH, Li W, Cao X

Stat3 is activated by phosphorylation on Tyr-705, which leads to dimer formation, nuclear translocation, and regulation of gene expression. Serine phosphorylation of Stat3 by mitogen-activated protein kinase has also been observed in cells responding to epidermal growth factor and shown to affect its tyrosine phosphorylation and transcriptional activity. Serine phosphorylation ...

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of Stat3 is also induced by interleukin-6 (IL-6) stimulation, which is shown to be independent of mitogen-activated protein kinase and sensitive to the Ser/Thr kinase inhibitor H7. In this study, we investigated whether protein kinase C (PKC) is the kinase that is induced and responsible for Stat3 serine phosphorylation by IL-6 stimulation and which isoform of PKCs is likely to be involved. Here, we report that Stat3 was specifically associated with PKC delta in vivo in an IL-6-dependent manner in several cell types. Furthermore, Stat3 was phosphorylated by PKC delta in vivo on Ser-727, which could be inhibited either by a specific PKC delta inhibitor or by a dominant-negative mutant of PKC delta. Finally, we showed that the phosphorylation of Stat3 by PKC delta led to a negative regulation of Stat3 DNA binding and transcriptional activity. These results indicate that PKC delta is likely to be the kinase that phosphorylates Stat3 in response to IL-6 stimulation and suggest a possible regulatory role of PKC delta on Stat3 function.

Date: Aug. 20, 1999

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