STAT3 mutations correlated with hyper-IgE syndrome lead to blockage of IL-6/STAT3 signalling pathway.

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dc.contributor.authorHe, Jianxin
dc.contributor.authorShi, Jie
dc.contributor.authorXu, Ximing
dc.contributor.authorZhang, Wenhua
dc.contributor.authorWang, Yuxin
dc.contributor.authorChen, Xing
dc.contributor.authorDu, Yuping
dc.contributor.authorZhu, Ning
dc.contributor.authorZhang, Jing
dc.contributor.authorWang, Qin
dc.contributor.authorYang, Jinbo
dc.date.accessioned2015-08-10T07:00:55Z
dc.date.available2015-08-10T07:00:55Z
dc.date.issued2012-06
dc.description.abstractOf all the causes identified for the disease hyper-immunoglobulinemia E syndrome (HIES), a homozygous mutation in tyrosine kinase2 (TYK2) and heterozygous mutations in STAT3 are implicated the defects in Jak/STAT signalling pathway in the pathogenesis of HIES. Mutations of STAT3 have been frequently clinically identified in autosomaldominant (AD) HIES patients’ cells, and therefore, the genotype of STAT3 has been associated with the phenotype of HIES. Here, we conducted studies on the functional loss of the seven specific STAT3 mutations correlated with ADHIES. Using STAT3-null human colon carcinoma cell line A4 cells, we generated seven mutants of STAT3 bearing single mutations clinically identified in AD-HIES patients’ cells and studied the functional loss of these mutants in IL- 6-Jak/STAT3 signalling pathway. Our results show that five STAT3 mutants bearing mutations in the DNA-binding domain maintain the phosphorylation of Tyr705 and the ability of dimerization while the other two with mutations in SH2 domain are devoid of the phosphorylation of Try705 and abrogate the dimerization in response to IL-6. The phosphorylation of Ser727 in these mutants shows diversity in response to IL-6. These mutations eventually converge on the abnormalities of the IL-6/Gp130/Jak2-mediated STAT3 transactivation on target genes, indicative of the dysregulation of JAK/STAT signalling present in HIES.en_US
dc.identifier.citationHe Jianxin, Shi Jie, Xu Ximing, Zhang Wenhua, Wang Yuxin, Chen Xing, Du Yuping, Zhu Ning, Zhang Jing, Wang Qin, Yang Jinbo. STAT3 mutations correlated with hyper-IgE syndrome lead to blockage of IL-6/STAT3 signalling pathway. Journal of Biosciences. 2012 Jun; 37 (2): 243-257.en_US
dc.identifier.urihttps://imsear.searo.who.int/handle/123456789/161668
dc.language.isoenen_US
dc.source.urihttps://www.ias.ac.in/jbiosci/jun2012/259.pdfen_US
dc.subjectHyper-IgE syndromeen_US
dc.subjectIL-6en_US
dc.subjectJak/STAT3 signallingen_US
dc.subjectSTAT3 mutationen_US
dc.titleSTAT3 mutations correlated with hyper-IgE syndrome lead to blockage of IL-6/STAT3 signalling pathway.en_US
dc.typeArticleen_US
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