SIGNALING BY THE CYTOKINE RECEPTOR SUPERFAMILY - JAKS AND STATS

A variety of cytokines, lymphokines and growth factors function by int eracting with receptors that are members of the cytokine receptor supe rfamily. These receptors share extracellular motifs and have limited s imilarity in their cytoplasmic domains. Although lacking catalytic dom ains, this family of receptors couples ligand binding with the inducti on of tyrosine phosphorylation. Recent studies have shown that this is mediated by members of the Janus kinase (JAK) family of cytoplasmic p rotein tyrosine kinases. JAKs physically associate with the membrane-p roximal region of the ligand-bound receptor, leading to their tyrosine phosphorylation and activation. The activated JAKs phosphorylate the receptors as well as cytoplasmic proteins belonging to a family of tra nscription factors called the signal transducers and activators of tra nscription (STATs), providing a novel signaling pathway that is shared by all members of the cytokine receptor superfamily.