Signal transducer and activator of transcription-3 serine phosphorylation by insulin is mediated by a Ras/Raf/MEK-dependent pathway

Brian P. Ceresa, Curt M. Horvath, Jeffrey E. Pessin

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

We recently reported that insulin stimulation results in the serine phosphorylation of STAT3 (signal transducer and activator of transcription- 3). In the present study, we identified serine 727 as the site of insulin- stimulated STAT3 serine phosphorylation. This phosphorylation event occurs independent of tyrosine phosphorylation. Furthermore, interleukin-6-induced tyrosine phosphorylation can occur independent of serine phosphorylation, demonstrating that these two phosphorylation pathways are mechanistically unrelated. Selective activation of the JNK and p38 family of mitogen- activated protein (MAP) kinases by anisomycin treatment did not result in the phosphorylation of STAT3. In contrast, activation of the ERK MAP kinase pathway with both insulin and osmotic shock resulted in the serine phosphorylation of STAT3. In addition, expression of a dominant-interfering Ras mutant (N17Ras) or treatment with the specific MEK inhibitor (PD98059) prevented the insulin stimulation of STAT3 serine phosphorylation. Blockade of ERK activation by expression of the MAP kinase phosphatase (MKP-1) had no effect on insulin-stimulated STAT3 serine phosphorylation. Together, these data demonstrate that the insulin-stimulated serine phosphorylation of STAT3 occurs by a MEK-dependent pathway that is independent of ERK activation.

Original languageEnglish (US)
Pages (from-to)4131-4137
Number of pages7
JournalEndocrinology
Volume138
Issue number10
DOIs
StatePublished - Jan 1 1997
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology

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