Characterization of insulin-like growth factor-1-induced activation of the JAK/STAT pathway in rat cardiomyocytes

Toshiyuki Takahashi, Keiichi Fukuda, Jing Pan, Hiroaki Kodama, Motoaki Sano, Shinji Makino, Takahiro Kato, Tomohiro Manabe, Satoshi Ogawa

研究成果: Article査読

45 被引用数 (Scopus)

抄録

This study was designed to investigate whether insulin-like growth factor-1 (IGF-1) transducers signaling through the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway in cardiomyocytes and to assess the upstream signals of serine and tyrosine phosphorylation of STAT family proteins. Primary cultured neonatal rat cardiomyocytes were stimulated with IGF-1 (10-8 mol/L). JAK1, but not JAK2 or Tyk2, was phosphorylated by IGF-1 as early as 2 minutes and peaked at 5 minutes. IGF-1 induced both tyrosine and serine phosphorylation of STAT1 and STAT3. Tyrosine phosphorylation of STAT1 peaked at 15 minutes and correlated with that of JAK1, whereas that of STAT3 was sustained up to 120 minutes and was dissociated activation of JAK1. Tyrosine phosphorylation of STAT3 was unaffected by the preincubation with CV11974 (AT1 blocker), TAK044 (endothelin-1 receptor blocker), RX435 (anti-gp130 blocking antibody), PD98058, wortmannin, EDTA, or KN62 but was significantly attenuated by BAPTA- AM and chelerythrine. The time course of a gel mobility shift of SIE (sis- inducing element) coincided with the phosphorylation of STAT3. Serine phosphorylation of STAT1 peaked at 30 minutes and that of STAT3 was observed from 5 to 60 minutes. These results indicated that (1) IGF-1 activated JAK1 but not JAK2 or Tyk2 in rat cardiomyocytes; (2) IGF-1 induced both tyrosine and serine phosphorylation of STAT1 and STAT3; and (3) the tyrosine phosphorylation of STAT3 was not caused by JAK1 alone, and protein kinase C and intracellular Ca2+ were required for phosphorylation.

本文言語English
ページ(範囲)884-891
ページ数8
ジャーナルCirculation research
85
10
DOI
出版ステータスPublished - 1999 11 12

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

フィンガープリント 「Characterization of insulin-like growth factor-1-induced activation of the JAK/STAT pathway in rat cardiomyocytes」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル