Signal transducers and activators of transcription STATs

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. 

Cytokine receptors, like receptor tyrosine kinases, have extracellular and intracellular domains and form dimers. However, after activation by an appropriate ligand, separate mobile protein tyrosine kinase molecules (JAK) are activated, resulting in phosphorylation of signal transducers and activation of transcription (STAT) molecules. STAT dimers then travel to the nucleus, where they regulate transcription. 

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... 

Blasius R, Reuter S, Henry E, Dicato M, Diederich M. 2006. Curcumin regulates signal transducer and activator of transcription (STAT) expression in K562 cells. Biochem Pharmacol 72 1547-1554. 

Fig. 6.5 Activation of the Jak/STAT pathway by angiotensin II. Binding of angiotensin II to the ATi receptor stimulates, via a G protein, the phosphorylation of janus family kinases (JAK). Jak2 participates in the phosphorylation and activation of signal transducers and activators of transcription (STAT) family members, which translocate to the nucleus and upregulate growth-linked genes.

The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway play a critical role in the signalling of a wide array of cytokines and growth factors, leading to various cellular functions, including proliferation, growth, haematopoiesis and immune response. 

Shigemura N, Miura H, Kusakabe Y, Hino A, Ninomiya Y (2003) Expression of leptin receptor (Ob-R) isoforms and signal transducers and activators of transcription (STATs) mRNAs in the mouse taste buds. Arch Histol Cytol 66 253-260 Shigemura N, Ohta R, Kusakabe Y, Miura H, Hino A, Koyano K, Nakashima K, Ninomiya Y (2004) Leptin modulates behavioral responses to sweet substances by influencing peripheral taste structures. Endocrinology 145 839-847... 

Klampfer, L. Signal transducers and activators of transcription (STATs) novel targets of chemopreventive and chemotherapeutic drugs. Curr. Cancer Drug Targets 2006, 6, 107-121. 

Expression of leptin receptor (Ob-R) isoforms and signal transducers and activators of transcription (STATs) mRNAs in the mouse taste buds. Arch Histol Cytol 66 253-260. 

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