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
Publication statusPublished - 1999 Nov 12

Fingerprint

Janus Kinases
Somatomedins
Transducers
Cardiac Myocytes
Phosphorylation
Tyrosine
Serine
STAT Transcription Factors
Endothelin A Receptors
Blocking Antibodies
Edetic Acid
Protein Kinase C
Gels

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Characterization of insulin-like growth factor-1-induced activation of the JAK/STAT pathway in rat cardiomyocytes. / Takahashi, Toshiyuki; Fukuda, Keiichi; Pan, Jing; Kodama, Hiroaki; Sano, Motoaki; Makino, Shinji; Kato, Takahiro; Manabe, Tomohiro; Ogawa, Satoshi.

In: Circulation Research, Vol. 85, No. 10, 12.11.1999, p. 884-891.

Research output: Contribution to journalArticle

@article{5f9934226c5a4be69e209b2afda2a64d,
title = "Characterization of insulin-like growth factor-1-induced activation of the JAK/STAT pathway in rat cardiomyocytes",
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.",
keywords = "Cardiomyocyte, Insulin-like growth factor-1, JAK, Signal transduction, STAT",
author = "Toshiyuki Takahashi and Keiichi Fukuda and Jing Pan and Hiroaki Kodama and Motoaki Sano and Shinji Makino and Takahiro Kato and Tomohiro Manabe and Satoshi Ogawa",
year = "1999",
month = "11",
day = "12",
language = "English",
volume = "85",
pages = "884--891",
journal = "Circulation Research",
issn = "0009-7330",
publisher = "Lippincott Williams and Wilkins",
number = "10",

}

TY - JOUR

T1 - Characterization of insulin-like growth factor-1-induced activation of the JAK/STAT pathway in rat cardiomyocytes

AU - Takahashi, Toshiyuki

AU - Fukuda, Keiichi

AU - Pan, Jing

AU - Kodama, Hiroaki

AU - Sano, Motoaki

AU - Makino, Shinji

AU - Kato, Takahiro

AU - Manabe, Tomohiro

AU - Ogawa, Satoshi

PY - 1999/11/12

Y1 - 1999/11/12

N2 - 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.

AB - 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.

KW - Cardiomyocyte

KW - Insulin-like growth factor-1

KW - JAK

KW - Signal transduction

KW - STAT

UR - http://www.scopus.com/inward/record.url?scp=0032745528&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032745528&partnerID=8YFLogxK

M3 - Article

C2 - 10559134

AN - SCOPUS:0032745528

VL - 85

SP - 884

EP - 891

JO - Circulation Research

JF - Circulation Research

SN - 0009-7330

IS - 10

ER -