The Janus protein tyrosine kinases in hematopoietic cytokine signaling

Abstract

Cytokines regulate cellular functions through their interaction with members of the cytokine receptor superfamily. These receptors couple ligand binding to induction of tyrosine phosphorylation through their association with the Janus protein tyrosine kinases (Jaks). Receptor dimerization induces Jak homo- or hetero-associations, autophosphorylation and activation of Jak catalytic activity. The activated Jaks are hypothesized to phosphorylate the receptors as well as a number of proteins involved in cellular signaling including SHC, the p85 subunit of PI 3-kinase, Vav and members of the Signal Transducers and Activators of Transcription (Stats) family of transcription factors. Receptor phosphorylation also allows association of hematopoietic cell phosphatase with the receptor complex, resulting in its down-regulation. Receptor mutants have allowed the identification of specific domains that are required for each function and their correlation with biological responses.