IL-6/STAT3 Signaling Pathways: Molecular Insights and Emerging Thereapeutic Targets

Abstract

The cytokine interleukin 6 (IL-6) has redundant biological activities in regulating the proliferation, differentiation, and function of various cell types. IL-6 regulates inflammation, immune responses, and hematopoiesis, as well as homeostasis of the nervous, renal, hormonal, and bone systems. IL-6 is also involved in tumorigenesis, including myeloma cell growth. The janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway is one of the key IL-6 signals both in normal and pathological conditions. In particular, STAT3 plays essential roles in mediating IL-6 signals, and its dysregulation can induce cancer and/or autoimmune diseases. In addition to biological and molecular mechanisms of IL-6-mediated signals, we have identified STAT3-interacting proteins, which regulate STAT3-mediated signals at various steps and mediate crosstalk between STAT3 and other intracellular signaling pathways. This review focuses on tyrosine kinase 2 (TYK2) and signal-transducing adapter protein-2 (STAP-2), followed by their potential as therapeutic targets in the development of novel treatments.