CYTOKINE RECEPTOR SIGNAL-TRANSDUCTION THROUGH JAK TYROSINE KINASES AND STAT TRANSCRIPTION FACTORS

Cytokines are the principal regulators of cell proliferation and diffe rentiation of hematopoietic cells and these responses are initiated th rough activation of hematopoietic cytokine receptors. Although the rec eptor intracellular domains lack any kinase domains, activation of cyt okine receptors lead to rapid induction of tyrosine phosphorylation. R ecently, cytokine receptors have been shown to associate with and acti vate 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 activatio n of intracellular signaling pathways. The best characterized substrat es for Jaks are the Stat transcription factors, which are crucial medi ators of cytokine-mediated gene responses, and, particularly, central determinants for the specificity in cytokine responses.