G alpha(12) specifically regulates COX-2 induction by sphingosine 1-phosphate - Role for JNK-dependent ubiquitination and degradation of I kappa B alpha
DC Field | Value | Language |
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dc.contributor.author | Ki, Sung Hwan | - |
dc.contributor.author | Choi, Min Jung | - |
dc.contributor.author | Lee, Chang Ho | - |
dc.contributor.author | Kim, Sang Geon | - |
dc.date.accessioned | 2022-12-21T09:36:15Z | - |
dc.date.available | 2022-12-21T09:36:15Z | - |
dc.date.created | 2022-08-26 | - |
dc.date.issued | 2007-01 | - |
dc.identifier.issn | 0021-9258 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/180600 | - |
dc.description.abstract | Cyclooxygenase-2 (COX-2) plays a critical role in vasodilatation and local inflammatory responses during platelet aggregation and thrombosis. Sphingosine 1-phosphate (S1P), a sphingolipid released from activated platelets, stimulates COX-2 induction and activates G-protein-coupled receptors coupled to G alpha family members. In this study, we investigated whether G alpha(12) family regulates COX-2 induction by S1P and investigated the molecular basis of this COX-2 regulation. Gene knock-out and chemical inhibitor experiments revealed that the S1P induction of COX-2 requires G alpha(12) but not G alpha(13), G alpha(q), or G alpha(i/o). The specific role of G alpha(12) in COX-2 induction by S1P was verified by promoter luciferase assay, G alpha(12) transfection, and knockdown experiments. Experiments using siRNAs specifically directed against S1P(1-5) showed that S1P(1), S1P(3), and S1P(5) are necessary for the full activation of COX-2 induction. Gel shift, immunocytochemistry, chromatin immuno-precipitation, and NF-kappa B site mutation analyses revealed the role of NF-kappa B inCOX-2 gene transcription by S1P. G alpha(12) deficiency did not affect S1P-mediated I kappa B alpha phosphorylation but abrogated I kappa B alpha ubiquitination and degradation. Moreover, the inhibition of S1P activation of JNK abolished I kappa B alpha ubiquitination. Consistently, JNK transfection restored the ability of S1P to degrade I kappa B alpha during G alpha(12) deficiency. S1P injection induced COX-2 in the lungs and livers of mice and increased plasma prostaglandin E-2, and these effects were prevented by G alpha(12) deficiency. Our data indicate that, of the G alpha proteins coupled to S1P receptors, G alpha(12) specifically regulates NF-kappa B-mediated COX-2 induction by S1P downstream of S1P(1), S1P(3), and S1P(5), in a process mediated by the JNK-dependent ubiquitination and degradation of I kappa B alpha. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | - |
dc.title | G alpha(12) specifically regulates COX-2 induction by sphingosine 1-phosphate - Role for JNK-dependent ubiquitination and degradation of I kappa B alpha | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Lee, Chang Ho | - |
dc.identifier.doi | 10.1074/jbc.M606080200 | - |
dc.identifier.scopusid | 2-s2.0-33847312302 | - |
dc.identifier.wosid | 000243451300044 | - |
dc.identifier.bibliographicCitation | JOURNAL OF BIOLOGICAL CHEMISTRY, v.282, no.3, pp.1938 - 1947 | - |
dc.relation.isPartOf | JOURNAL OF BIOLOGICAL CHEMISTRY | - |
dc.citation.title | JOURNAL OF BIOLOGICAL CHEMISTRY | - |
dc.citation.volume | 282 | - |
dc.citation.number | 3 | - |
dc.citation.startPage | 1938 | - |
dc.citation.endPage | 1947 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | Y | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.subject.keywordPlus | NITRIC-OXIDE SYNTHASE | - |
dc.subject.keywordPlus | LIGASE ITCH | - |
dc.subject.keywordPlus | C/EBP-BETA | - |
dc.subject.keywordPlus | TNF-ALPHA | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | RECEPTOR | - |
dc.subject.keywordPlus | CYCLOOXYGENASE-2 | - |
dc.subject.keywordPlus | CELLS | - |
dc.subject.keywordPlus | PHOSPHORYLATION | - |
dc.subject.keywordPlus | KINASE | - |
dc.identifier.url | https://www.sciencedirect.com/science/article/pii/S0021925820721927?via%3Dihub | - |
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