Description
JAK-STAT pathway is a main intracellular cascade initiated in response to cytokine signaling. In mammals, four Jak and seven Stat family members mediate the action of almost 40 cytokines receptors including the receptor for leptin. While leptin is not a cytokine, its receptor bears structural similarity to class I cytokine receptor family. The current model of the pathway states that receptor activation of Jak leads to phosphorylation of tyrosine residues on the cytoplasmic domain of the receptor, subsequent recruitment of Stat to the receptor–Jak complex, phosphorylation of Stat followed by Stat dimerization and translocation to the nucleus to activate specific gene expression. Various receptors may utilize particular Jak -Stat combinations. In the cytoplasm, the action of Jak-Stat is opposed by Socs family members some of which represent a feedback inhibitory loop as their expression is under the control of Stat. Of note is the fact that Socs proteins negatively regulate both leptin and insulin signaling pathways. Several tyrosine phosphatases are aso implicated in inhibiting Jak-Stat pathway. In the nucleus, the action of Jak-Stat is opposed by members of the Pias family of proteins. Despite a good understanding of the overall scheme of the pathway, the details of individual receptor/Jak-Stat pathways, the evolution of the various Jak-Stat pathway ‘isoforms’, the mechanism and regulation of their actions are issues that remain to be elucidated. The diagram depicts a generic JAK-STAT signaling pathway.
