STAT proteins

The first two STAT proteins were identified in the interferon system.

"Prolactin signaling through stat proteins"

Usually found in immunoglobulin proteins, they are also present in Stat proteins of the cytokine pathway.

Kinase activity phosphorylates STAT proteins which then are recruited by transcription factors.

The resulting phosphotyrosines attract STAT proteins.

The STAT proteins dimerize and enter the nucleus to act as transcription factors to alter gene expression.

STAT proteins were originally described as latent cytoplasmic transcription factors that require phosphorylation for nuclear retention.

Of the proteins recruited to type I cytokine receptors STAT proteins remain the best studied.

The unphosphorylated STAT proteins shuttles between cytosol and the nucleus waiting for its activation signal.

JAK kinase phosphorylates STAT proteins, which dissociate from the receptor and translocate to the nucleus to regulate gene expression.

Similarly to nuclear receptors and to other transcription factors, STAT proteins can interact with coactivators to modulate their transcriptional activity [ 9 10 11 12 ] .

One such receptor-associated tyrosine kinase is Janus kinase (JAK), many of whose effects are mediated by STAT proteins.

Gene 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 tumour surveillance.

STAT proteins have several functional domains, including an N-terminal interaction domain, a central DNA-binding domain, an SH2 domain, and the C-terminal transactivation domain.

Once STAT proteins are activated by tyrosine-phosphorylation, form homo or heterodimers that are translocated to the nucleus, where they can bind to specific sequences in the DNA, thereby stimulating gene transcription.