STAT1


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STAT1

A gene on chromosome 2q32.2 that encodes a member of the STAT family of transcription factors, which are phosphorylated by receptor-associated kinases in response to cytokines and growth factors. The STAT1 protein product is activated by IFN-alpha, IFN-gamma, EGF, PDGF and IL6; it mediates the expression of various genes, which is important for cell viability in response to different cell stimuli and pathogens.
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After stimulation with cytokines (e.g., IFN-[gamma]), STAT1 molecules are phosphorylated, dimerized, and translocated into the nucleus for gene expression and then dephosphorylated and released to the cytoplasm [12].
The STAT1 pathway is one of the signal transduction pathways that controls T-bet expression (Afkarian et al.
Cutting edge: role of IL-27/WSX-1 signaling for induction of T-bet through activation of STAT1 during initial Th1 commitment.
Using mice bred specially to express a mutated form of STAT1 which is limited to forming single STAT1 units, the Nottingham team has demonstrated that this abolishes the function of some interferons while leaving others largely unaffected.
The STAT family of transcription factors consists of STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, and STAT6 [16-18].
Further, we have observed in asthmatic compared with non-asthmatic ASM cells that NF[kappa]B activation is stronger and STAT1 activation is weaker in response to the three cytokines combined (cytomix) [35], which may underlie the small inhibitory effect of histamine in the non-asthmatic ASM cells.
TIE2 activation induces the phosphorylation of STAT1, STAT3, and STAT5A/5B and their subsequent translocation into nucleus to induce the expression of the cell cycle inhibitor cyclin-dependent kinase inhibitor 1A (p21) [38].
IL-23 phosphorylates STAT1, 3, 4, and 5, but STAT4 activation, which is essential to produce IFN[gamma], is not strong compared to that in IL-12 stimulation [19].
As shown in Table 4 the incubation of skin cells with TSc resulted in a promotion of the phosphorylation of STAT upstream proteins Fyn, Lyn, Src, and Yes and additionally of the most STATs including STAT1, 2, 3, 5a, and 5a/b in NHEK and NHDF.
The signal transducer and activator (STAT) proteins STAT1 and STAT4 induce the expression of the Th1-specific transcription factor T-box expressed in T cells (T-bet) [13].
Singh, "IFN-gamma synergistically enhances LPS signalling in alveolar macrophages from COPD patients and controls by corticosteroid-resistant STAT1 activation," British Journal of Pharmacology, vol.