JAK-STAT signaling pathway
The JAK-STAT signaling pathway is a chain of interactions between proteins in a cell, and is involved in processes such as immunity, cell division, cell death, and tumour formation. The pathway communicates information from chemical signals outside of a cell to the cell nucleus, resulting in the activation of genes through a process called transcription. There are three key parts of JAK-STAT signalling: Janus kinases (JAKs), signal transducer and activator of transcription proteins (STATs), and receptors (which bind the chemical signals). Janus kinaseJanus kinase or tyrosine-protein kinase JAK (JAK) are nonreceptor tyrosine kinases which transduces cytokine-mediated signals via the JAK-STAT pathway. The JAK-STAT pathway transmits signals through the cell membrane to DNA promoters thus causing transcription. The name JAK is derived from Just Another Kinase. JAK proteins contain 2 phosphate-transfer domains, one with kinase activity using a phosphotyrosine (PTyr) and the other a pseudokinase domain which negatively regulates the kinase domain. JAK contains seven Janus homology domains named JH1-7. JAK family members are JAK1, JAK2, JAK3 and TYK2[1]. Jak3 inhibitors are tested in treatment of autoimmune diseases and transplant rejection[2]. Mutations in Jak2 are associated with chronic myeloproliferative neoplasms, polycythemia vera, essential thrombocytosis and primary myelofibrosis[3]. Mutations in Jak3 are associated with immune deficiency. Jak2 containing phosphotyrosine binds the thienopyridine potent inhibitor in the ATP-binding pocket[4]. Water molecules shown as red spheres. Signal transducer and activator of transcription proteins (STATs)
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