Activation of JAK-STAT and MAP Kinases by Leukemia Inhibitory Factor Through gp130 in Cardiac Myocytes

• DOI: 10.1161/01.cir.94.10.2626
• Publication Date: 2012-06-12T00:34:42Z
• Authors: Keita Kunisada; Hisao Hirota; Yasushi Fujio; Hideo Matsui; Yoshihiko Tani; Keiko Yamauchi-Ta...; Tadamitsu Kishimoto
• Keywords: Glycoprotein 130

Background Interleukin (IL)-6–related cytokines share gp130 as the signal-transducing protein. Downstream of gp130, two pathways have been recognized, Janus kinase–signal transducer and activator transcription (JAK-STAT) pathway Ras–mitogen-activated protein kinase (MAPK) pathway. To determine whether these signaling through are present in cardiac myocytes, we examined their activation by using leukemia inhibitory factor (LIF), which is a member IL-6 cytokine family. Methods Results Lysates from neonatal rat myocytes were immunoprecipitated with anti-gp130, anti-JAK1, or anti-STAT3 antibody blotted anti-phosphotyrosine antibody. Tyrosine phosphorylation JAK1, STAT3 was observed after LIF stimulation myocytes. MAPKs maximally activated 5 minutes stimulation. Furthermore, anti-gp130 significantly inhibited LIF-induced STAT3, MAPKs. examine also adult heart vivo, injected intravenously into 6-week-old mouse, subsequently. treatment. Conclusions These results demonstrate for first time that JAK-STAT MAPK downstream rapidly both vitro vivo. Activation constitutes novel