Cytokine G-protein signaling crosstalk in cardiomyocytes: attenuation of Jak-STAT activation by endothelin-1.

摘要: The IL-6-related cytokines, LIF and cardiotrophin-1, are important growth promoting cardioprotective agents for cardiomyocytes. However, factors that regulate their actions in the heart poorly understood. In this study, we tested hypothesis endothelin-1, a peptide hormone produces pattern of cardiac hypertrophy distinct from modulates LIF-induced signaling Upon binding or receptor alpha subunit (LIFRalpha) dimerizes with gp130, leading to activation constitutively associated Jak1 proteins LIFRalpha-gp130 tyrosine phosphorylation. We found pretreatment neonatal rat ventricular myocytes endothelin-1 rapidly inhibited LIFRalpha phosphorylation activation. This effect on LIFalpha was attenuated by MEK1 inhibitor, PD98059, implicating involvement ERK kinases. Radioligand studies showed inhibition resulted reduction cell surface LlFRalpha levels. Additionally, reduce STAT3 activation, as indexed Y705 Finally, were shown induce opposite patterns induced rapid, robust phosphorylation; produced delayed, modest increase, initially decreased Overall our findings indicate acts temper cytokine cardiomyocytes, particular