Membrane receptor signaling by various ligands, including interferons and growth hormones such as EGF, induces activation of JAK kinases which then leads to tyrosine phosphorylation of the various Stat transcription factors. Stat1 and Stat2 are induced by IFN-α and form a heterodimer which is part of the ISGF3 transcription factor complex. Although early reports indicate Stat3 activation by EGF and IL-6, it has been shown that Stat3β appears to be activated by both while Stat3α is activated by EGF, but not by IL-6. Highest expression of Stat4 is seen in testis and myeloid cells. IL-12 has been identified as an activator of Stat4. Stat5 has been shown to be activated by Prolactin and by IL-3. Stat6 is involved in IL-4 activated signaling pathways. Mutations in the STAT1 molecule can be gain of function (GOF) or loss of function (LOF). Both of them can cause different phenotypes and symptoms. Recurring common infections are frequent in both GOF and LOF mutations. In humans STAT1 has been particularly under strong purifying selection when populations shifted from hunting and gathering to farming, because this went along with a change in the pathogen spectrum. STAT1 loss of function, therefore STAT1 deficiency can have many variants. There are two main genetic impairments that can cause response to interferons type I and III. First there can be autosomal recessive partial or even complete deficiency of STAT1. That causes intracellular bacterial diseases or viral infections and impaired IFN a, b, g and IL27 responses are diagnosed. In partial form there can also be found high levels of IFNg in blood serum. When tested from whole blood, monocytes do not respond to BCG and IFNg doses with IL-12 production. In complete recessive form there is a very low response to anti-viral and antimycotical medication. Second, partial STAT1 deficiency can also be an autosomal dominant mutation; phenotypically causing impaired IFNg responses and causing patients to suffer with selective intracellular bacterial diseases (MSMD).
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Număr Catalog 992-ET1606-39CategorieAfaceri și industrie > Știință și laboratorFurnizorHUABIOGentaurDimensiune100ulTipsingle
