Caveolin-2 regulation of STAT3 transcriptional activation in response to insulin.
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.
Department of Biochemistry, Gyeongsang National University, Jinju 660-701, Republic of Korea.
Hayeong
H
Kwon
Kyuho
K
Jeong
Eun Mi
EM
Hwang
Jae-Yong
JY
Park
Seong-Geun
SG
Hong
Wan-Sung
WS
Choi
Yunbae
Y
Pak
D000818:Animals; D051243:Caveolin 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D015151:Immunoblotting; D047468:Immunoprecipitation; D007328:Insulin / Q000494:pharmacology*; D008156:Luciferases; D009154:Mutation / Q000235:genetics; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000378:metabolism; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects*; D014443:Tyrosine / Q000378:metabolism
D051243:Caveolin 2; D007004:Hypoglycemic Agents; D007328:Insulin; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; D019000:Phosphotyrosine; D014443:Tyrosine; D008156:Luciferases