Interferon Janus kinases

Cytokine receptors that couple to the JAK-STAT Pathway decode the signaling though hematopoietic cytokines (erythropoietin, thrombopoietin, colony-stimulating factors), prolactin, growth hormone, the a-, (3- and y- interferons, and a number of immunomodulatory interleukins [3], They form homodimetic or heterodimeric receptor complexes, which after ligandbinding recruit and activate isotypes of Janus kinases (JAKs). Activated JAKs in turn... 

The leptin signal is transduced by a mechanism also used by receptors for interferon and growth factors, the JAIC-STAT system (Fig. 23-34 see Fig. 12-9). The leptin receptor, which has a single transmembrane segment, dimerizes when leptin binds to the extracellular domain of two monomers. Both monomers are phos-phorylated on a Tyr residue of the intracellular domain by a Janus kinase (JAK). The -Tyr residues become docking sites for three proteins that are signal transducers and activators of transcription (STATs 3, 5, and 6, sometimes called fat-STATS). The docked STATs are then phosphorylated on Tyr residues by the... 

These include the receptors for erythropoietin, somatotropin, and interferons. Their receptors are membrane spanning and on activation can activate a distinctive set of cytoplasmic tyrosine kinases (Janus kinases [JAKs]). JAKs phosphory-late signal transducers and activators of transcription (STAT) molecules. STATs dimerize and then dissociate, cross the nuclear membrane, and modulate gene transcription. 

Sakamoto H, Yasukawa H, Masuhara M, Tanimura S, Sasaki A, Yuge K, Ohtsubo M, Ohtsuka A, Fujita T, Ohta T, Furukawa Y, Iwase S, Yamada H, Yoshimura A A Janus kinase inhibitor, JAB, is an interferon-y-inducible gene and confers resistance to interferons. Blood 1998 92 1668-1676. 

The receptors for cytokines and interferons are the starting point for signal transduction chains that bring about an activation of transcription factors. The signaling pathway involves the Janus protein kinase and Stat transcription factors (see 11.1.4). Phosphoty-rosine-SH2 interactions are also involved in several steps of signal transduction here. 

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