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Jak Stat Signaling Pathway


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Jak Stat Signaling Pathway

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The JAK-STAT signaling pathway transmits information from extracellular chemical signals regulating growth, survival, differentiation, and pathogen resistance. The JAK-STAT signalling cascade consists of three main components: a cell surface receptor, a Janus kinase (JAK) and two Signal Transducer and Activator of Transcription (STAT) proteins. Disrupted or dysregulated JAK-STAT functionality can result in immune deficiency syndromes and cancers. The cell surface receptors, usually cytokines, such as interferon, interleukin, and growth factors, activate associated JAKs, increasing their kinase activity. In mammals, the JAK family comprises four members: JAK1, JAK2, JAK 3 and Tyk2. Activated JAKs then phosphorylate tyrosine residues on the receptor, creating binding sites for proteins possessing SH2 domains. SH2 domain containing STATs are recruited to the receptor where they are also tyrosine-phosphorylated by JAKs. STATs are latent transcription factors that reside in the cytoplasm until activated. These activated STATs form hetero- or homodimers and translocate to the cell nucleus where they induce transcription of target genes. The phosphorylated sites on the receptor and Jaks serve as docking sites for the SH2-containing Stats, such as Stat3, and for SH2-containing proteins and adaptors that link the receptor to MAP kinase, PI3K/Akt, and other cellular pathways.

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