STAT6

STAT6 is the acronym for "Signal Transducer and Activator of Transcription 6", a transcription factor that belongs to the family of Signal Transducer and Activator of Transcription (STAT) proteins, which comprises 7 members:

STAT1-STAT4, STAT5A, STAT5B and STAT6. The proteins of the STAT family transmit signals from a receptor complex to the cell nucleus and activate gene expression.

STAT6 is activated by growth factors and cytokines, in particular by interleukin-4 and interleukin-13.

The protein is structurally similar to the other STAT proteins and consists of the N-terminal domain, the DNA-binding domain, the SH3-like domain, the SH2 domain and the transactivation domain (TAD)[7].

STAT proteins are activated by Janus family tyrosine kinases (JAKs) in response to cytokine exposure. STAT6 is activated by the cytokines interleukin-4 (IL-4) and interleukin-13 (IL-13) with their receptors, both of which contain the α-subunit of the IL-4 receptor (IL-4Rα). Tyrosine phosphorylation of STAT6 after stimulation by IL-4 leads to the formation of STAT6 homodimers that bind specific DNA elements via a DNA-binding domain.

Function: The STAT6-mediated signaling pathway is required for the development of T helper type 2 (Th2) cells and the Th2 immune response. The STAT6 protein is critical for IL4-mediated biological responses.

Activation of the STAT6 signaling pathway is important for macrophage function and is required for activation of the M2 subtype of macrophages.

The STAT6 protein also regulates other transcription factors such as Gata3, which is an important regulator of Th2 differentiation. STAT6 is also required for the development of interleukin-9-secreting T cells.

STAT6 also plays a critical role in Th2 inflammatory responses in the lung, including clearance of parasitic infections and in the pathogenesis of asthma.

STAT6 interacts with:

• CREB-binding protein
• EP300
• IRF4
• NFKB1
• Nuclear receptor coactivator 1
• SND1

1. Robinson DR et al (2013) Identification of recurrent NAB2-STAT6 gene fusions in solitary fibrous tumor by integrative sequencing. Nat Genet 45:180-185.
2. Xian RR et al (2020) CREBBP and STAT6 co-mutation and 16p13 and 1p36 loss define the t(14;18)-negative diffuse variant of follicular lymphoma. Blood Cancer J 10(6):69.
3. Yildiz M et al (2015) Activating STAT6 mutations in follicular lymphoma. Blood 125:668-679.