Entrez 6775 | Ensembl ENSG00000138378 | |
Aliases STAT4, SLEB11, signal transducer and activator of transcription 4 External IDs OMIM: 600558 MGI: 103062 HomoloGene: 20679 GeneCards: STAT4 | ||
Signal transducer and activator of transcription 4 (STAT4) is a transcription factor belonging to the STAT 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.
Contents
Structure
Human as well murine STAT4 genes lie next to STAT1 gene locus suggesting that the genes arose by gene duplication. 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.
Expression
Distribution of STAT4 is restricted to myeloid cells, thymus and testis. In resting human 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 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 cytokines (IFN-γ, TNF), receptors (IL18R1, IL12rβ2, IL18RAP), and signaling factors (MYD88).