The JAK-STAT-SOCS Signaling Cascade

Abstract

The JAK-STAT pathway is the central intracellular signal transduction cascade initiated by ligand binding to numerous growth factor and cytokine receptors, and since its discovery two decades ago it has been the subject of extensive investigation. The pathway is negatively regulated by the SOCS family proteins, which restrict the extent of the cytokine response, thus preventing excessive and deleterious inflammatory and immune signaling. There are now many examples of human mutations and disease conditions where the JAK-STAT-SOCS axis is perturbed, and we have witnessed the advent of JAK inhibitors in the clinic. This review explores our current understanding of how this unique pathway funct..