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

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)884-891
Number of pages8
JournalCirculation research
Volume85
Issue number10
DOIs
Publication statusPublished - 1999 Nov 12

Keywords

  • Cardiomyocyte
  • Insulin-like growth factor-1
  • JAK
  • STAT
  • Signal transduction

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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