STAT4

STAT4 is a is_associated_with::transcription factor belonging to the Signal Transducer and Activator of Transcription protein family. It is required for the development of Th1 cells from naive CD4+ T cells and IFN-γ production in response to IL-12.

Structure
Human as well murine STAT4 genes lie next to is_associated_with::STAT1 gene locus suggesting that the genes arose by is_associated_with::gene duplication. is_associated_with::STAT proteins have several functional domains, including an N-terminal interaction domain, a central is_associated_with::DNA-binding domain, an is_associated_with::SH2 domain, and the C-terminal transactivation domain.

Expression
Distribution of STAT4 is restricted to myeloid cells, is_associated_with::thymus and testis. In resting human is_associated_with::T cells it is expressed at very low levels, but its production is amplified by PHA stimulation.

Activation
Two chains of IL-12 receptor form heterodimer after IL-12 binding and activate the receptor associated JAK kinases, termed JAK2 and TYK2. Stat4 is phosphorylated by these tyrosine kinases, homodimerizes via its is_associated_with::SH2 domain and translocates into nucleus to activate gene transcription.

Target genes
STAT4 binds to hundreds of sites in the genome, among others to the promoters of genes for is_associated_with::cytokines (IFN-γ, TNF), receptors (is_associated_with::IL18R1, IL12rβ2, is_associated_with::IL18RAP), and signaling factors (is_associated_with::MYD88).