Signal Transducer and Activator of Transcription

STAT1 is activated by various ligands including cytokines, IFN-a, IFN-y, IL-4, IL-5, IL-13, growth factors and hormones. It has four conserved domains N-terminal, C-terminal, SH2 domain and DNA-binding domain, which is typical of all STAT family members. The SH2 domain is distinct for each STAT and a stable SH2-phosphotyrosine bond is formed after the SH2 domain binds to its specific phosphotyrosine domain. This SH2-pTyr bond is responsible for STAT activation 

STAT Ligand STAT Deficiency-Associated Human Disease 

STAT1 IFN Alzheimer s disease, cancer, celiac disease, ischemic heart disease, Inflammatory Bowel Disease (IBD), rheumatoid arthritis 

STAT4 IL-12 Chronic obstructive pulmonary disease (COPD), rheumatoid arthritis 

STAT5a PRL Cancer, diabetes, ischemic heart disease 

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Ihle, J. 1996. STATs signal transducers and activators of transcription. Cell 84, 331-334. 

JAKs and signal transducers and activators of transcription (STATs) are functionally analogous with IRS and PI3K. JAKs are physically associated with a cell surface receptor (e.g. for leptin, erythropoietin (EPO), growth factors or cytokines) STATs are free monomeric proteins within the cytosol but following phosphorylation by a JAK, individual proteins dimerize and then move into the nucleus of the cell where they control gene expression. 

Leptin signalling is via monomeric receptors in the brain. A short-form of the leptin receptor (Lep-R) is required to transport the hormone across the blood-brain barrier and a long-form Lep-R is located in the hypothalamus. The long-form is functionally linked with a particular type of receptor-associated tyrosine kinase called Janus kinase (JAK, see Section 4.7) whose function is to phosphorylate a STAT (signal transducer and activator of transcription) protein a similar mechanism to that often associated with signalling by inflammatory cytokines. 

STAT-3 Signal transducer and activator of transcription-3 VEGFR Vascular endothelial growth factor receptor... 

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