The JAK-STAT signaling pathway plays a central role in transducing stress and growth signals in the hypertrophic heart. Unlike most signal transducers, JAKs and STATs signal in a number of different ways, both within the JAK-STAT pathway and in collaboration with other signaling pathways. In this review, we discuss how IL-6 activates cells lacking IL-6 receptors through trans-signaling and examine JAK-STAT pathway interaction with GPCR-linked pathways both within and between cells. Finally, we discuss recent studies showing how the JAK-STAT pathway can intersect with a general transcriptional regulatory mechanism to effect transcription of STAT-dependent stress response genes.
Keywords: Il-6 trans-signaling; JAK-STAT signaling pathway; angiotensin II; autocrine signaling; cardiac hypertrophy; cardiac lineage protein-1; endothelin-1; paracrine signaling; transcription elongation factor b; αB-crystallin.