Cytokine receptor signal transduction through Jak tyrosine kinases and Stat transcription factors

Cytokines are the principal regulators of cell proliferation and differentiation of hematopoietic cells and these responses are initiated through activation of hematopoietic cytokine receptors. Although the receptor intracellular domains lack any kinase domains, activation of cytokine receptors lead to rapid induction of tyrosine phosphorylation. Recently, cytokine receptors have been shown to associate with and activate members of the cytoplasmic Jak tyrosine kinase family. Activation of Jak kinases leads to phosphorylation of several signaling proteins and thereby couples ligand-mediated receptor stimulation to activation of intracellular signaling pathways. The best characterized substrates for Jaks are the Stat transcription factors, which are crucial mediators of cytokine-mediated gene responses, and, particularly, central determinants for the specificity in cytokine responses.