The role of JAK/STAT signaling pathway and its inhibitors in diseases

Int Immunopharmacol. 2020 Mar:80:106210. doi: 10.1016/j.intimp.2020.106210. Epub 2020 Jan 20.

Abstract

The JAK/STAT signaling pathway is an universally expressed intracellular signal transduction pathway and involved in many crucial biological processes, including cell proliferation, differentiation, apoptosis, and immune regulation. It provides a direct mechanism for extracellular factors-regulated gene expression. Current researches on this pathway have been focusing on the inflammatory and neoplastic diseases and related drug. The mechanism of JAK/STAT signaling is relatively simple. However, the biological consequences of the pathway are complicated due to its crosstalk with other signaling pathways. In addition, there is increasing evidence indicates that the persistent activation of JAK/STAT signaling pathway is closely related to many immune and inflammatory diseases, yet the specific mechanism remains unclear. Therefore, it is necessary to study the detailed mechanisms of JAK/STAT signaling in disease formation to provide critical reference for clinical treatments of the diseases. In this review, we focus on the structure of JAKs and STATs, the JAK/STAT signaling pathway and its negative regulators, the associated diseases, and the JAK inhibitors for the clinical therapy.

Keywords: JAK/STAT pathway and diseases; JAK/STAT signaling pathway; JAKs inhibitors and diseases; Negative regulators.

Publication types

  • Review

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Disease Models, Animal
  • Humans
  • Immune System Diseases / drug therapy*
  • Immune System Diseases / immunology
  • Immune System Diseases / pathology
  • Inflammation / drug therapy*
  • Inflammation / immunology
  • Inflammation / pathology
  • Janus Kinases / antagonists & inhibitors
  • Janus Kinases / metabolism*
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • STAT Transcription Factors / antagonists & inhibitors
  • STAT Transcription Factors / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / immunology*

Substances

  • Cytokines
  • Protein Kinase Inhibitors
  • STAT Transcription Factors
  • Janus Kinases