JAK-STAT

JAKs (Janus Kinase; EC 2.7.10.2; 4 types identified) and STATs (Signal Transducer and Activator of Transcription; 7 types identified) are critical components of many cytokine receptor systems, regulating growth, survival, differentiation and pathogen resistance. (Cytokine) receptor-bound STATs phosphorylated by JAKs dimerize and translocate into the nucleus to regulate target gene transcription. In most cases, a specific JAK-STAT combination has been paired with a specific member of the cytokine receptor family, and this information translated into cell-type specific patterns of cytokine responsiveness and gene expression. Members of the suppressor of cytokine signaling (SOCS) protein family dampen receptor signaling via homologous or heterologous feedback regulation[1],[2]. Consequently, Janus kinase mutations are major molecular events in human hematological malignancies[3].


[1] The JAK-STAT Signaling Pathway: Input and Output Integration. P.J. Murray. J. Immunol. 2007, 178, 2623-2629.
[2] A Road Map for Those Who Don't Know JAK-STAT. D.S. Aaronson, C.M. Horvath. Science 2002, 296, 1653-1655.
[3] Cytokine receptor signaling through the Jak-Stat-Socs pathway in disease. O'Sullivan LA, Liongue C, Lewis RS, Stephenson SE, Ward AC. Mol. Immunol. 2007, 44, 2497–506.

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