Caveolin-2 regulation of STAT3 transcriptional activation in response to insulin

Hayeong Kwon, Kyuho Jeong, Eun Mi Hwang, Jae Yong Park, Seong Geun Hong, Wan Sung Choi, Yunbae Pak

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The regulatory function of caveolin-2 in signal transducer and activator of transcription 3 (STAT3) signaling by insulin was investigated. Insulin-induced increase in phosphorylation of STAT3 was reduced by caveolin-2 siRNA. Mutagenesis studies identified that phosphorylation of tyrosines 19 and 27 on caveolin-2 is required for the STAT3 activation. Caveolin-2 Y27A mutation decreased insulin-induced phosphorylation of STAT3 interacting with caveolin-2. pY27-Caveolin-2 was required for nuclear translocation of pY705-STAT3 in response to insulin. In contrast, caveolin-2 Y19A mutation influenced neither the phosphorylation of STAT3 nor nuclear translocation of pY705-STAT3. pY19-Caveolin-2, however, was essential for insulin-induced DNA binding of pS727-STAT3 and STAT3-targeted gene induction in the nucleus. Finally, insulin-induced transcriptional activation of STAT3 depended on phosphorylation of both 19 and 27 tyrosines. Together, our data reveal that phosphotyrosine-caveolin-2 is a novel regulator for transcriptional activation of STAT3 in response to insulin.

Original languageEnglish
Pages (from-to)1325-1333
Number of pages9
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1793
Issue number7
DOIs
Publication statusPublished - 2009 Jul 1

Keywords

  • Caveolin-2 siRNA
  • Caveolin-2 tyrosine variant mutant
  • Insulin
  • STAT3 transcriptional activation
  • pS727-STAT3
  • pY19-Caveolin-2
  • pY27-Caveolin-2
  • pY705-STAT3

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Caveolin-2 regulation of STAT3 transcriptional activation in response to insulin'. Together they form a unique fingerprint.

  • Cite this