{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1362262943973866880.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.4049/jimmunol.166.6.3855"}},{"identifier":{"@type":"URI","@value":"https://academic.oup.com/jimmunol/article-pdf/166/6/3855/62537897/3855.pdf"}}],"dc:title":[{"@value":"Inhibition of the MEK/ERK Signaling Pathway Blocks a Subset of B Cell Responses to Antigen"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:title>Abstract</jats:title>\n               <jats:p>Signal transduction initiated by B cell Ag receptor (BCR) cross-linking plays an important role in the development and activation of B cells. Therefore, considerable effort has gone into determining the biochemical signaling events initiated by the BCR and delineating which events participate in specific biological responses to Ag. We used two inhibitors of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK) 1 and MEK2, PD98059, and U0126, to assess the role the Ras-mitogen-activated protein kinase pathway plays in several BCR-induced responses. PD98059 or U0126 treatment substantially inhibited the BCR-induced activation of the extracellular signal-regulated kinase (ERK) forms of mitogen-activated protein kinase in the immature B cell line WEHI-231, in immature splenic B cells, and in mature splenic B cells. However, MEK-ERK inhibition did not block BCR-induced growth arrest or apoptosis of WEHI-231 cells or apoptosis of immature splenic B cells, indicating that the MEK-ERK pathway is not required for these events. In contrast, PD98059 and U0126 treatment did inhibit the up-regulation of specific BCR-induced proteins, including the transcription factor Egr-1 in WEHI-231 and mature splenic B cells, and the CD44 adhesion molecule and CD69 activation marker in mature splenic B cells. Moreover, both inhibitors suppressed BCR-induced proliferation of mature splenic B cells, in the absence and in the presence of IL-4. Therefore, activation of the MEK-ERK pathway is necessary for a subset of B cell responses to Ag.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380303973030875777","@type":"Researcher","foaf:name":[{"@value":"James D Richards"}],"jpcoar:affiliationName":[{"@value":"Department of Microbiology and Immunology, G. W. Hooper Foundation, University of California , San Francisco, CA 94143"}]},{"@id":"https://cir.nii.ac.jp/crid/1380303973030875779","@type":"Researcher","foaf:name":[{"@value":"Shaival H Davé"}],"jpcoar:affiliationName":[{"@value":"Department of Microbiology and Immunology, G. W. Hooper Foundation, University of California , San Francisco, CA 94143"}]},{"@id":"https://cir.nii.ac.jp/crid/1380303973030875776","@type":"Researcher","foaf:name":[{"@value":"Chih-Hao G Chou"}],"jpcoar:affiliationName":[{"@value":"Department of Microbiology and Immunology, G. W. Hooper Foundation, University of California , San Francisco, CA 94143"}]},{"@id":"https://cir.nii.ac.jp/crid/1380303973030875778","@type":"Researcher","foaf:name":[{"@value":"Alusha A Mamchak"}],"jpcoar:affiliationName":[{"@value":"Department of Microbiology and Immunology, G. W. Hooper Foundation, University of California , San Francisco, CA 94143"}]},{"@id":"https://cir.nii.ac.jp/crid/1380303973030875780","@type":"Researcher","foaf:name":[{"@value":"Anthony L DeFranco"}],"jpcoar:affiliationName":[{"@value":"Department of Microbiology and Immunology, G. W. Hooper Foundation, University of California , San Francisco, CA 94143"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00221767"},{"@type":"EISSN","@value":"15506606"}],"prism:publicationName":[{"@value":"The Journal of Immunology"}],"dc:publisher":[{"@value":"Oxford University Press (OUP)"}],"prism:publicationDate":"2001-03","prism:volume":"166","prism:number":"6","prism:startingPage":"3855","prism:endingPage":"3864"},"reviewed":"false","dc:rights":["https://academic.oup.com/pages/standard-publication-reuse-rights"],"url":[{"@id":"https://academic.oup.com/jimmunol/article-pdf/166/6/3855/62537897/3855.pdf"}],"createdAt":"2014-04-20","modifiedAt":"2025-03-30","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360285708633907072","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"TRPC3 amplifies B-cell receptor-induced ERK signalling via protein kinase D-dependent Rap1 activation"}]},{"@id":"https://cir.nii.ac.jp/crid/1360565170325047168","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Thy28 partially prevents apoptosis induction following engagement of membrane immunoglobulin in WEHI-231 B lymphoma cells"}]},{"@id":"https://cir.nii.ac.jp/crid/1360565170865839744","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Transgenic Overexpression of G5PR That Is Normally Augmented in Centrocytes Impairs the Enrichment of High-Affinity Antigen-Specific B Cells, Increases Peritoneal B-1a Cells, and Induces Autoimmunity in Aged Female Mice"}]},{"@id":"https://cir.nii.ac.jp/crid/1360846640910843776","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"ERK1/2 antagonize AMPK-dependent regulation of FcεRI-mediated mast cell activation and anaphylaxis"}]},{"@id":"https://cir.nii.ac.jp/crid/1360848661467895168","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Trametinib Attenuates Delayed Rejection and Preserves Thymic Function in Rat Lung Transplantation"}]},{"@id":"https://cir.nii.ac.jp/crid/1360848661476543232","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"The MEK inhibitor trametinib separates murine graft-versus-host disease from graft-versus-tumor effects"}]},{"@id":"https://cir.nii.ac.jp/crid/1360849939298579200","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Inferring the transcriptional regulatory mechanism of signal‐dependent gene expression <i>via</i> an integrative computational approach"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.4049/jimmunol.166.6.3855"},{"@type":"CROSSREF","@value":"10.1042/bj20150596_references_DOI_OojpSDS5lugxB773dGNKCu7sNMN"},{"@type":"CROSSREF","@value":"10.1016/j.jaci.2014.05.001_references_DOI_OojpSDS5lugxB773dGNKCu7sNMN"},{"@type":"CROSSREF","@value":"10.2478/s11658-011-0034-8_references_DOI_OojpSDS5lugxB773dGNKCu7sNMN"},{"@type":"CROSSREF","@value":"10.4049/jimmunol.1102774_references_DOI_OojpSDS5lugxB773dGNKCu7sNMN"},{"@type":"CROSSREF","@value":"10.1165/rcmb.2018-0188oc_references_DOI_OojpSDS5lugxB773dGNKCu7sNMN"},{"@type":"CROSSREF","@value":"10.1172/jci.insight.86331_references_DOI_OojpSDS5lugxB773dGNKCu7sNMN"},{"@type":"CROSSREF","@value":"10.1002/1873-3468.13757_references_DOI_OojpSDS5lugxB773dGNKCu7sNMN"}]}