19592641

Source:http://linkedlifedata.com/resource/pubmed/id/19592641

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Predicate	Object
rdf:type	pubmed:Citation
lifeskim:mentions	umls-concept:C0031715, umls-concept:C0337112, umls-concept:C0546816, umls-concept:C0851285, umls-concept:C1149207, umls-concept:C1335877, umls-concept:C1524075, umls-concept:C1882417, umls-concept:C2003941
pubmed:issue	3
pubmed:dateCreated	2009-7-21
pubmed:abstractText	Several commonly occurring polymorphisms in the IL-4R(alpha) have been associated with atopy in humans; the Q576R and the S503P polymorphisms reside in the cytoplasmic domain, whereas the I50 to V50 polymorphism resides in the extracellular domain of the IL-4R(alpha). The effects of these polymorphisms on signaling remain controversial. To determine the effect of the polymorphisms on IL-4 signaling in human cells, we stably transfected the human monocytic cell line U937 with murine IL-4R(alpha) cDNA bearing the I or V at position 50 and the P503/R576 double mutant. Each form of the murine IL-4R(alpha) mediated tyrosine phosphorylation of STAT6 in response to murine IL-4 treatment similar to the induction of tyrosine phosphorylation by human IL-4 signaling through the endogenous human IL-4R(alpha). After IL-4 removal, tyrosine-phosphorylated STAT6 rapidly decayed in cells expressing I50 or P503R576 murine IL-4Ralpha. In contrast, STAT6 remained significantly phosphorylated for several hours after murine IL-4 withdrawal in cells expressing the V50 polymorphism. This persistence in tyrosine-phosphorylated STAT6 was associated with persistence in CIS mRNA expression. Blocking IL-4 signaling during the decay phase using the JAK inhibitor AG490 or the anti-IL-4R(alpha) Ab M1 abrogated the persistence of phosphorylated STAT6 observed in the V50-IL-4R(alpha)-expressing cells. These results indicate that the V50 polymorphism promotes sustained STAT6 phosphorylation and that this process is mediated by continued engagement of IL-4R(alpha), suggesting enhanced responses of V50 IL-4R when IL-4 is limiting.
pubmed:grant	http://linkedlifedata.com/resource/pubmed/grant/AI038985, http://linkedlifedata.com/resource/pubmed/grant/R01 AI038985-10, http://linkedlifedata.com/resource/pubmed/grant/R01 AI038985-11, http://linkedlifedata.com/resource/pubmed/grant/R01 AI038985-12A1, http://linkedlifedata.com/resource/pubmed/grant/R01 AI038985-13, http://linkedlifedata.com/resource/pubmed/grant/R01 AI038985-14, http://linkedlifedata.com/resource/pubmed/grant/R01 AI038985-15, http://linkedlifedata.com/resource/pubmed/grant/T32 HL007698-12, http://linkedlifedata.com/resource/pubmed/grant/T32 HL007698-13, http://linkedlifedata.com/resource/pubmed/grant/T32 HL007698-14, http://linkedlifedata.com/resource/pubmed/grant/T32 HL007698-15, http://linkedlifedata.com/resource/pubmed/grant/T32 HL007698-16, http://linkedlifedata.com/resource/pubmed/grant/T32HL007698
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pubmed:language	eng
pubmed:journal	http://linkedlifedata.com/resource/pubmed/journal/2985117R
pubmed:citationSubset	AIM
pubmed:chemical	http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-4, http://linkedlifedata.com/resource/pubmed/chemical/STAT6 Transcription Factor, http://linkedlifedata.com/resource/pubmed/chemical/STAT6 protein, human
pubmed:status	MEDLINE
pubmed:month	Aug
pubmed:issn	1550-6606
pubmed:author	pubmed-author:BoothbyMark RMR, pubmed-author:FordAndrew QAQ, pubmed-author:HellerNicola MNM, pubmed-author:KeeganAchsah DAD, pubmed-author:StephensonLindaL
pubmed:issnType	Electronic
pubmed:day	1
pubmed:volume	183
pubmed:owner	NLM
pubmed:authorsComplete	Y
pubmed:pagination	1607-16
pubmed:dateRevised	2011-9-26
pubmed:meshHeading	pubmed-meshheading:19592641-Cell Line, pubmed-meshheading:19592641-Humans, pubmed-meshheading:19592641-Hypersensitivity, pubmed-meshheading:19592641-Mutation, Missense, pubmed-meshheading:19592641-Phosphorylation, pubmed-meshheading:19592641-Polymorphism, Genetic, pubmed-meshheading:19592641-RNA, Messenger, pubmed-meshheading:19592641-Receptors, Interleukin-4, pubmed-meshheading:19592641-STAT6 Transcription Factor, pubmed-meshheading:19592641-Signal Transduction
pubmed:year	2009
pubmed:articleTitle	An atopy-associated polymorphism in the ectodomain of the IL-4R(alpha) chain (V50) regulates the persistence of STAT6 phosphorylation.

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