Signal transducer and activator of transcription 3 (STAT3) is a transcription factor which is encoded by the STAT3 gene.
It is a member of the STAT protein family.
Chromosome 17.
In response to cytokines and growth factors, it is phosphorylated by receptor-associated Janus kinases (JAK), form and translocates to the cell nucleus where they act as transcription activators.
STAT3 becomes activated after phosphorylation of tyrosine in response to such ligands as interferons, epidermal growth factor (EGF), Interleukin (IL-)5 and IL-6.
Activation of STAT3 may occur via phosphorylation of serine by Mitogen-activated protein kinases (MAPK) and through c-src non-receptor tyrosine kinase.
It mediates the expression of a number of genes in response to cell stimuli, and plays a key role in many cellular processes such as cell growth and apoptosis.
At early stages of development, STAT3 activation is required for self-renewal of embryonic stem cells (ESCs).
STAT3 is essential for the differentiation of the TH17 helper T cells.
TH17 helper T cells have been implicated in a variety of autoimmune diseases.
STAT3 gene loss of function mutations result in Hyperimmunoglobulin E syndrome.
Hyperimmunoglobulin E syndrome is
associated with recurrent infections as well as disordered bone and tooth development.
Gain-of-function mutations in the STAT3 gene cause multi-organ early onset auto-immune diseases; such as thyroid disease, diabetes, intestinal inflammation, and low blood counts.
STAT3 activation is associated with various human cancers and commonly suggests poor prognosis.
STAT3 has anti-apoptotic as well as proliferative effects.
A tumor suppressor role of STAT3 has also been reported.
Increased activity of STAT3 in cancer cells changes the function of protein complexes that control expression of inflammatory genes, increasing tumor activity and capacity for metastasis.
STAT3 has been shown to interact with:
EGFR
JAK1
mTOR
Among many other biological pathways.