Protein kinase C delta associates with the interleukin-6 receptor subunit glycoprotein (gp) 130 via Stat3 and enhances Stat3-gp130 interaction - PubMed (original) (raw)

. 2002 Dec 20;277(51):49134-42.

doi: 10.1074/jbc.M206727200. Epub 2002 Oct 1.

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Protein kinase C delta associates with the interleukin-6 receptor subunit glycoprotein (gp) 130 via Stat3 and enhances Stat3-gp130 interaction

Veronica Novotny-Diermayr et al. J Biol Chem. 2002.

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Abstract

The transcriptional regulation of Stat proteins is controlled through their C-terminal domains, which harbor both a tyrosine phosphorylation site, required for dimerization and subsequent nuclear translocation, and a serine phosphorylation site, required for maximum transcriptional activity. Previously, we reported that protein kinase Cdelta (PKCdelta) phosphorylates and interacts with Stat3 in an interleukin (IL)-6-dependent manner. In this study, we further characterized this interaction, and investigated the potential role of such an interaction. We show here that the catalytic domain of PKCdelta interacts with the Src homology 2 domain and part of the adjacent C-terminal transactivation domain of Stat3. This interaction, which does not seem to involve a classical phosphotyrosine SH2-mediated binding, however, significantly enhances the interaction of Stat3 and the IL-6 receptor subunit glycoprotein (gp) 130, which is the initial step for Stat3 activation by IL-6. Expression of a dominant negative PKCdelta or depletion of the endogenous PKCdelta by phorbol 12-myristate 3-acetate treatment abrogates the association of Stat3 with gp130. At the same time, PKCdelta is recruited to gp130 via association with Stat3, which may facilitate its phosphorylation on the gp130 receptor. Finally, we identified Thr-890, a putative PKC phosphorylation site on gp130, to be critical for the effect of PKCdelta. Our data indicate that PKCdelta plays important regulatory roles in IL-6 signaling.

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