View source for STAT protein

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==Overview==
[[Image:Stat domain structure.png|thumb|350px|left|Domains and covalent modification sites of STAT proteins.]]
The '''Signal Transducers and Activator of Transcription (STAT) protein'''s regulate many aspects of [[cell growth]], survival and [[differentiation]].  The [[transcription factor]]s of this family are activated by the Janus Kinase [[JAK]] and dysregulation of this pathway is frequently observed in primary tumors and leads to increased [[angiogenesis]], enhanced survival of [[tumors]] and [[immunosuppression]]. [[Knockout]] studies have provided evidence that STAT proteins are involved in the development and function of the [[immune system]] and play a role in maintaining [[immune tolerance]] and tumor surveillance. 

==STAT family==
The first two STAT proteins were identified in the interferon system 

The seven mammalian STAT family members identified are: [[STAT1]], [[STAT2]], [[STAT3]], [[STAT4]], [[STAT5]] a and b, and [[STAT6]].  

STAT1 homodimers are involved in type II interferon signalling, and binds to the '''GAS''' (Interferon-'''G'''amma '''A'''ctivated '''S'''equence) promoter to induce expression of '''ISG''' ('''I'''nterferon '''S'''timulated '''G'''enes).  In type I interferon signaling, STAT1-STAT2 heterodimer combines with '''IRF'''9 ('''I'''nterferon '''R'''esponse '''F'''actor) to form '''ISGF'''3 ('''I'''nterferon '''S'''timulated '''G'''ene '''F'''actor), which binds to the '''ISRE''' ('''I'''nterferon Stimulated Response Element) promoter to induce ISG expression.

==Function==
STAT proteins were originally described as latent [[cytoplasmic]] transcription factors that require [[phosphorylation]] for nuclear retention. The unphosphorylated STAT proteins shuttles between cytosol and the nucleus waiting for its activation signal. Once the activated transcription factors reaches the nucleus it binds to consensus DNA-recognition motif called gamma activated sites (GAS) in the [[promoter]] region of [[cytokine]] [[inducible gene]]s and activates transcription of these genes. 

==Activation==
Extracellular binding of [[cytokine]]s induces activation of the intracellular Janus kinase that phosphorylates a specific tyrosine residue in the STAT protein which promotes the [[dimerization]] of STAT monomers via their [[SH2 domain]]. The phosphorylated dimer is then actively transported in the nucleus via [[importin|importin a/b]] and RanGDP  complex. Once inside the nucleus the active STAT dimer binds to cytokine inducible promoter regions of genes containing gamma activated site (GAS) motif and activate [[Transcription (genetics)|transcription]] of these genes. The STAT protein can be dephosphorylated by nuclear [[phosphatases]] which leads to inactivation of STAT and the transcription factor becomes transported out of the nucleus by [[exportin]] crm1/RanGTP.

==See also==
*[[JAK-STAT pathway]]
*[[DNA-binding protein]]

==References==
<div class="references-small">
{{reflist|2}}
</div>

==Additional images==
<gallery>
 Image:Jakstat pathway.svg|Key steps of the [[JAK-STAT pathway]]
</gallery>

==External links==
* {{MeshName|STAT+Transcription+Factors}}

{{Transcription factors}}
{{Adaptor proteins}}

[[Category:Gene expression]]
[[Category:Immune system]]
[[Category:Oncology stub]]
[[Category:Proteins]]
[[Category:Transcription factors]]
[[Category:Signal transduction]]

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