Can the protective actions of JAK-STAT in the heart be exploited therapeutically?
Kurdi M; Booz GW Division of Molecular Cardiology, Cardiovascular Research Institute, College of Medicine, The Texas A&M University System Health Science Center, College Station, TX 76504, USA. Activation of the transcription factor signal transducers and activators of transcription (STAT) 3 is a defining feature of the interleukin (IL)-6 family of cytokines, which include IL-6, leukemia inhibitory factor, and cardiotrophin-1. These cytokines, as well as STAT3 activation, have been shown to be protective for cardiac myocytes and necessary for ischemia preconditioning. However, the mechanisms that regulate IL-6-type cytokine signaling in cardiac myocytes are largely unexplored. We propose that the protective character of IL-6-type cytokine signaling in cardiac myocytes is determined principally by three mechanisms: redox status of the nonreceptor tyrosine kinase Janus kinase 1 (JAK) 1 that activates STAT3, phosphorylation of STAT3 within the transcriptional activation domain on serine 7
