STATs cells

Originally discovered as DNA-binding proteins that mediate interferon signaling, recent data demonstrated that STAT1 can also exert constitutive functions in the nucleus, which do not require STAT activation with tyrosine phosphorylation. Cells lacking STAT1 are... 

Besides the cytokine receptors that lack intrinsic kinase activity but have associated JAK kinases, STAT proteins can be activated by a variety of G-protein coupled receptors and growth factor receptors with intrinsic tyrosine kinase activity (for example EGF, PDGF, CSF-1, and angiotensin receptor). Increasing evidence suggests a critical role for STAT family members in oncogenesis and aberrant cell proliferation. Constitutively activated STATs have been found in many transformed cell lines and a wide variety of human tumor entities. Numerous non-receptor tyrosine kinases and viral oncoproteins, such as v-Src, v-Abl, v-Sis, and v-Eyk, have been identified to induce DNA-binding activity of STAT proteins. 

Akira S (1999) Functional roles of STAT family proteins lessons from knockout mice. Stem Cells 17 138-146... 

The cytokine leptin is secreted by adipocytes (fat cells) in proportion to the size of the adipose dq>ot and circulates via the bloodstream to the brain, where it ultimately affects feeding behavior, endocrine systems including reproductive function and, at least in rodents, energy expenditure. The major effect of Lqrtin is on the hy-pothalamous, where it suppresses appetite and hence food intake. Leptin exerts its effects via binding to the leptin receptor in the brain (specifically in the hypothalamus), which activates the JAK-STAT Pathway. 

In chronic myelogenous leukemia (CML) as well as in a subset of acute lymphoblastic leukemia (ALL) Bcr-Abl, a fusion protein of c-Abl and the breakpoint cluster region (bcr), is expressed in the cytosol of leukemic cells. This fusion protein forms homo-oligomeric complexes that display elevated kinase activity and is the causative molecular abnormality in CML and certain ALL. The transforming effect of Bcr-Abl is mediated by numerous downstream signaling pathways, including protein kinase C (PKC), Ras-Raf-ERK MAPK, JAK-STAT (see below), and PI3-kinase pathways. 

Honda, H. Sugiyama, H. Saito, I., and Kobayashi, T., High cell density culture of Rhodococcus rhodochrous by pH-stat feeding and dibenzothiophene degradation. Journal of Fermentation and Bioengineering, 1998. 85(3) pp. 334—338. 

STATs are differentially distributed in various cells/tissues. STATs 1,2 and 3 seem to be present in most cell types, all be it at varying concentrations. Tissue distribution of STATs 4 and 5 is more limited. 

Table 8.6 Ligands which, upon binding to their cell surface receptors, are known to promote activation of one or more STATs. (The STATs activated are also shown.) This list, though representative, is not exhaustive...

A number of proteins that inhibit the JAK-STAT function have also been identified. These include members of the so-called SOCS/Jab/Cis family and the PIAS family of regulatory proteins. Several appear to function by inhibiting the activation of various STATs, although the mechanisms by which this is achieved remain to be elucidated in detail. The JAK-STAT pathway likely does not function in isolation within the cell. JAKs are believed to activate elements of additional signalling pathways, and STATs are also likely activated by factors other than JAKs. As such, there may be considerable crosstalk between various JAK- and/or STAT-dependent signalling pathways. 

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

Lau, F. and Horvath, C. 2002. Mechanisms of type I interferon cell signalling and STAT-mediated transcriptional responses. Mount Sinai Journal of Medicine 69(3), 156-168. 

O Shea, J.J., Gadina, M., and Schreiber, R.D. 2002. Cytokine signalling in 2002 new surprises in the JAK/STAT pathway. Cell 109, S121-S131. 

This list is not intended to be comprehensive but to indicate the wide array of neuronal proteins regulated by phosphorylation. Some of the proteins are specific to neurons but most are present in many cell types in addition to neurons and are included because their multiple functions in the nervous system include the regulation of neuron-specific phenomena. Not included are the many phosphoproteins present in diverse tissues, including brain, that play a role in generalized cellular processes, such as intermediary metabolism, and that do not appear to play a role in neuron-specific phenomena. NMDA, N-methyl-D-aspartate CREB, cAMP response element-binding proteins STAT, signal-transducing activators of transcription ... 

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