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 language | English |
|---|---|
| Pages (from-to) | 1325-1333 |
| Number of pages | 9 |
| Journal | Biochimica et Biophysica Acta - Molecular Cell Research |
| Volume | 1793 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 2009 Jul 1 |
| Externally published | Yes |
Fingerprint
Keywords
- Caveolin-2 siRNA
- Caveolin-2 tyrosine variant mutant
- Insulin
- pS727-STAT3
- pY19-Caveolin-2
- pY27-Caveolin-2
- pY705-STAT3
- STAT3 transcriptional activation
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology
Cite this
Caveolin-2 regulation of STAT3 transcriptional activation in response to insulin. / Kwon, Hayeong; Jeong, Kyuho; Hwang, Eun Mi; Park, Jae-Yong; Hong, Seong Geun; Choi, Wan Sung; Pak, Yunbae.
In: Biochimica et Biophysica Acta - Molecular Cell Research, Vol. 1793, No. 7, 01.07.2009, p. 1325-1333.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Caveolin-2 regulation of STAT3 transcriptional activation in response to insulin
AU - Kwon, Hayeong
AU - Jeong, Kyuho
AU - Hwang, Eun Mi
AU - Park, Jae-Yong
AU - Hong, Seong Geun
AU - Choi, Wan Sung
AU - Pak, Yunbae
PY - 2009/7/1
Y1 - 2009/7/1
N2 - 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.
AB - 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.
KW - Caveolin-2 siRNA
KW - Caveolin-2 tyrosine variant mutant
KW - Insulin
KW - pS727-STAT3
KW - pY19-Caveolin-2
KW - pY27-Caveolin-2
KW - pY705-STAT3
KW - STAT3 transcriptional activation
UR - http://www.scopus.com/inward/record.url?scp=67649397307&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67649397307&partnerID=8YFLogxK
U2 - 10.1016/j.bbamcr.2009.04.015
DO - 10.1016/j.bbamcr.2009.04.015
M3 - Article
C2 - 19427337
AN - SCOPUS:67649397307
VL - 1793
SP - 1325
EP - 1333
JO - Biochimica et Biophysica Acta - Molecular Cell Research
JF - Biochimica et Biophysica Acta - Molecular Cell Research
SN - 0167-4889
IS - 7
ER -