| pubmed-article:19287004 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:19287004 | lifeskim:mentions | umls-concept:C1334291 | lld:lifeskim |
| pubmed-article:19287004 | lifeskim:mentions | umls-concept:C0033684 | lld:lifeskim |
| pubmed-article:19287004 | lifeskim:mentions | umls-concept:C1335280 | lld:lifeskim |
| pubmed-article:19287004 | lifeskim:mentions | umls-concept:C1519726 | lld:lifeskim |
| pubmed-article:19287004 | lifeskim:mentions | umls-concept:C1417014 | lld:lifeskim |
| pubmed-article:19287004 | lifeskim:mentions | umls-concept:C0205360 | lld:lifeskim |
| pubmed-article:19287004 | lifeskim:mentions | umls-concept:C0851285 | lld:lifeskim |
| pubmed-article:19287004 | pubmed:issue | 20 | lld:pubmed |
| pubmed-article:19287004 | pubmed:dateCreated | 2009-5-11 | lld:pubmed |
| pubmed-article:19287004 | pubmed:abstractText | Previously we have shown that tyrosine 718 of ASK1 when phosphorylated is critical for SOCS1 binding and SOCS1-mediated degradation of ASK1. However, the kinase and phosphatase responsible for phosphorylation and dephosphorylation of ASK1 at Tyr-718 are unknown. In this study, we identified JAK2 and SHP2 as a Tyr-718-specific kinase and phosphatase, respectively. Interferon-gamma (IFN-gamma) induced degradation of ASK1 in normal but not in SOCS1-KO endothelial cells (EC). IFN-gamma-induced tyrosine phosphorylation of ASK1 at Tyr-718 was blocked by a JAK2-specific inhibitor. IFN-gamma enhanced the association between JAK2 and ASK1, and the ASK1-JAK2 complex was labile and was stabilized by the proteasomal inhibitor MG132. Furthermore, JAK2, but not JAK1, directly bound to and phosphorylated ASK1 at Tyr-718, leading to an enhanced association of ASK1 with SOCS1 and subsequent ASK1 degradation. Next, we showed that overexpression of the SH2-containing protein-tyrosine phosphatase-2 (SHP2) augmented, whereas a phosphatase-inactive mutant of SHP2 inhibited, TNF-induced ASK1 dephosphorylation. SHP2 associated with ASK1 in response to tumor necrosis factor in EC. An SHP-2 substrate-trapping mutant formed a complex with tyrosine-phosphorylated ASK1, suggesting that ASK1 is a direct SHP2 substrate. Moreover, SHP2 wild type, but not a catalytically inactive mutant, dissociated SOCS1 from ASK1. IFN-gamma-induced ASK1 Tyr(P)-718 was enhanced in mouse EC deficient in SHP2 (SHP2-KO). In contrast, tumor necrosis factor-induced dephosphorylation of ASK1 at Tyr(P)-718 and activation of ASK1-JNK signaling, as well as EC apoptosis, are significantly reduced in SHP2-KO EC. Our data suggest that JAK2-SOCS1 and SHP2 reciprocally regulate ASK1 phosphorylation and stability in response to cytokines. | lld:pubmed |
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| pubmed-article:19287004 | pubmed:language | eng | lld:pubmed |
| pubmed-article:19287004 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19287004 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:19287004 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:19287004 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:19287004 | pubmed:month | May | lld:pubmed |
| pubmed-article:19287004 | pubmed:issn | 0021-9258 | lld:pubmed |
| pubmed-article:19287004 | pubmed:author | pubmed-author:WebbS LSL | lld:pubmed |
| pubmed-article:19287004 | pubmed:author | pubmed-author:ChenHongH | lld:pubmed |
| pubmed-article:19287004 | pubmed:author | pubmed-author:BennettAnton... | lld:pubmed |
| pubmed-article:19287004 | pubmed:author | pubmed-author:HeYunY | lld:pubmed |
| pubmed-article:19287004 | pubmed:author | pubmed-author:ZhangHaifengH | lld:pubmed |
| pubmed-article:19287004 | pubmed:author | pubmed-author:YuLuyangL | lld:pubmed |
| pubmed-article:19287004 | pubmed:author | pubmed-author:QinLingfengL | lld:pubmed |
| pubmed-article:19287004 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:19287004 | pubmed:day | 15 | lld:pubmed |
| pubmed-article:19287004 | pubmed:volume | 284 | lld:pubmed |
| pubmed-article:19287004 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:19287004 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:19287004 | pubmed:pagination | 13481-8 | lld:pubmed |
| pubmed-article:19287004 | pubmed:dateRevised | 2011-11-2 | lld:pubmed |
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| pubmed-article:19287004 | pubmed:meshHeading | pubmed-meshheading:19287004... | lld:pubmed |
| pubmed-article:19287004 | pubmed:year | 2009 | lld:pubmed |
| pubmed-article:19287004 | pubmed:articleTitle | JAK2 and SHP2 reciprocally regulate tyrosine phosphorylation and stability of proapoptotic protein ASK1. | lld:pubmed |
