{"@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/1360004239495949952.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.3390/ijms20061346"}},{"identifier":{"@type":"URI","@value":"https://www.mdpi.com/1422-0067/20/6/1346/pdf"}},{"identifier":{"@type":"PMID","@value":"30884895"}}],"resourceType":"学術雑誌論文(journal article)","dc:title":[{"@value":"Roles of Cyclic AMP Response Element Binding Activation in the ERK1/2 and p38 MAPK Signalling Pathway in Central Nervous System, Cardiovascular System, Osteoclast Differentiation and Mucin and Cytokine Production"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>There are many downstream targets of mitogen-activated protein kinase (MAPK) signalling that are involved in neuronal development, cellular differentiation, cell migration, cancer, cardiovascular dysfunction and inflammation via their functions in promoting apoptosis and cell motility and regulating various cytokines. It has been reported that cyclic AMP response element-binding protein (CREB) is phosphorylated and activated by cyclic AMP signalling and calcium/calmodulin kinase. Recent evidence also points to CREB phosphorylation by the MAPK signalling pathway. However, the specific roles of CREB phosphorylation in MAPK signalling have not yet been reviewed in detail. Here, we describe the recent advances in the study of this MAPK-CREB signalling axis in human diseases. Overall, the crosstalk between extracellular signal-related kinase (ERK) 1/2 and p38 MAPK signalling has been shown to regulate various physiological functions, including central nervous system, cardiac fibrosis, alcoholic cardiac fibrosis, osteoclast differentiation, mucin production in the airway, vascular smooth muscle cell migration, steroidogenesis and asthmatic inflammation. In this review, we focus on ERK1/2 and/or p38 MAPK-dependent CREB activation associated with various diseases to provide insights for basic and clinical researchers.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380004239495950081","@type":"Researcher","foaf:name":[{"@value":"Yasuhiko Koga"}],"jpcoar:affiliationName":[{"@value":"Department of Allergy and Respiratory Medicine, Gunma University Graduate School of Medicine, 3-39-15 sho-wa machi Maebashi, Gunma 371-8511, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004239495949954","@type":"Researcher","foaf:name":[{"@value":"Hiroaki Tsurumaki"}],"jpcoar:affiliationName":[{"@value":"Department of Allergy and Respiratory Medicine, Gunma University Graduate School of Medicine, 3-39-15 sho-wa machi Maebashi, Gunma 371-8511, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004239495949953","@type":"Researcher","foaf:name":[{"@value":"Haruka Aoki-Saito"}],"jpcoar:affiliationName":[{"@value":"Department of Allergy and Respiratory Medicine, Gunma University Graduate School of Medicine, 3-39-15 sho-wa machi Maebashi, Gunma 371-8511, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004239495950208","@type":"Researcher","foaf:name":[{"@value":"Makiko Sato"}],"jpcoar:affiliationName":[{"@value":"Department of Allergy and Respiratory Medicine, Gunma University Graduate School of Medicine, 3-39-15 sho-wa machi Maebashi, Gunma 371-8511, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004239495949952","@type":"Researcher","foaf:name":[{"@value":"Masakiyo Yatomi"}],"jpcoar:affiliationName":[{"@value":"Department of Allergy and Respiratory Medicine, Gunma University Graduate School of Medicine, 3-39-15 sho-wa machi Maebashi, Gunma 371-8511, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004239495950080","@type":"Researcher","foaf:name":[{"@value":"Kazutaka Takehara"}],"jpcoar:affiliationName":[{"@value":"Department of Allergy and Respiratory Medicine, Gunma University Graduate School of Medicine, 3-39-15 sho-wa machi Maebashi, Gunma 371-8511, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1420001326206006016","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"10344938"},{"@type":"NRID","@value":"1000010344938"},{"@type":"NRID","@value":"9000020795591"},{"@type":"NRID","@value":"9000401514896"},{"@type":"NRID","@value":"9000000449738"},{"@type":"NRID","@value":"9000024805425"},{"@type":"NRID","@value":"9000387479506"},{"@type":"NRID","@value":"9000045697970"},{"@type":"NRID","@value":"9000398987372"},{"@type":"NRID","@value":"9000020425480"},{"@type":"NRID","@value":"9000253628728"},{"@type":"NRID","@value":"9000014374097"},{"@type":"NRID","@value":"9000310332595"},{"@type":"NRID","@value":"9000253619271"},{"@type":"NRID","@value":"9000415311724"},{"@type":"NRID","@value":"9000020800840"},{"@type":"NRID","@value":"9000379610584"},{"@type":"NRID","@value":"9000391591942"},{"@type":"NRID","@value":"9000301716464"},{"@type":"NRID","@value":"9000404157757"},{"@type":"NRID","@value":"9000021619447"},{"@type":"NRID","@value":"9000248966571"},{"@type":"NRID","@value":"9000021231827"},{"@type":"NRID","@value":"9000021491923"},{"@type":"NRID","@value":"9000253618969"},{"@type":"NRID","@value":"9000257946799"},{"@type":"NRID","@value":"9000387479915"},{"@type":"NRID","@value":"9000381459574"},{"@type":"NRID","@value":"9000021603729"},{"@type":"NRID","@value":"9000021619206"},{"@type":"NRID","@value":"9000405883657"},{"@type":"NRID","@value":"9000414353783"},{"@type":"NRID","@value":"9000021230690"},{"@type":"NRID","@value":"9000253614379"},{"@type":"NRID","@value":"9000021933451"},{"@type":"NRID","@value":"9000321627783"},{"@type":"NRID","@value":"9000253624968"},{"@type":"NRID","@value":"9000006222581"},{"@type":"NRID","@value":"9000020424775"},{"@type":"NRID","@value":"9000402244536"},{"@type":"NRID","@value":"9000405705246"},{"@type":"NRID","@value":"9000345429413"},{"@type":"NRID","@value":"9000312254367"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/read0097822"}],"foaf:name":[{"@value":"Takeshi Hisada"}],"jpcoar:affiliationName":[{"@value":"Gunma University Graduate School of Health Sciences, 3-39-22 sho-wa machi Maebashi, Gunma 371-8514, Japan"}]}],"publication":{"publicationIdentifier":[{"@type":"EISSN","@value":"14220067"}],"prism:publicationName":[{"@value":"International Journal of Molecular Sciences"}],"dc:publisher":[{"@value":"MDPI AG"}],"prism:publicationDate":"2019-03-17","prism:volume":"20","prism:number":"6","prism:startingPage":"1346"},"reviewed":"false","dc:rights":["https://creativecommons.org/licenses/by/4.0/"],"url":[{"@id":"https://www.mdpi.com/1422-0067/20/6/1346/pdf"}],"createdAt":"2019-03-18","modifiedAt":"2025-10-11","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=Central%20Nervous%20System","dc:title":"Central Nervous System"},{"@id":"https://cir.nii.ac.jp/all?q=MAP%20Kinase%20Signaling%20System","dc:title":"MAP Kinase Signaling System"},{"@id":"https://cir.nii.ac.jp/all?q=Mucins","dc:title":"Mucins"},{"@id":"https://cir.nii.ac.jp/all?q=Osteoclasts","dc:title":"Osteoclasts"},{"@id":"https://cir.nii.ac.jp/all?q=Cell%20Differentiation","dc:title":"Cell Differentiation"},{"@id":"https://cir.nii.ac.jp/all?q=Review","dc:title":"Review"},{"@id":"https://cir.nii.ac.jp/all?q=Cardiovascular%20System","dc:title":"Cardiovascular System"},{"@id":"https://cir.nii.ac.jp/all?q=Cardiovascular%20Diseases","dc:title":"Cardiovascular Diseases"},{"@id":"https://cir.nii.ac.jp/all?q=Central%20Nervous%20System%20Diseases","dc:title":"Central Nervous System Diseases"},{"@id":"https://cir.nii.ac.jp/all?q=Animals","dc:title":"Animals"},{"@id":"https://cir.nii.ac.jp/all?q=Cytokines","dc:title":"Cytokines"},{"@id":"https://cir.nii.ac.jp/all?q=Humans","dc:title":"Humans"},{"@id":"https://cir.nii.ac.jp/all?q=Phosphorylation","dc:title":"Phosphorylation"},{"@id":"https://cir.nii.ac.jp/all?q=Cyclic%20AMP%20Response%20Element-Binding%20Protein","dc:title":"Cyclic AMP Response Element-Binding Protein"}],"project":[{"@id":"https://cir.nii.ac.jp/crid/1040282256977375616","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"18K08382"},{"@type":"JGN","@value":"JP18K08382"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18K08382/"}],"notation":[{"@language":"ja","@value":"重症難治性喘息への挑戦　抗炎症性脂質メディエーターの作用解析から創薬へ向けた研究"},{"@language":"en","@value":"Challenges in Overcoming Severe Asthma ~Research of anti-inflammatory lipid mediators toward drug discovery~"}]},{"@id":"https://cir.nii.ac.jp/crid/1040282256977387392","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"18K08404"},{"@type":"JGN","@value":"JP18K08404"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18K08404/"}],"notation":[{"@language":"ja","@value":"気道炎症におけるプロトン感知性受容体OGR1を介した新規吸入薬開発への挑戦"},{"@language":"en","@value":"Challenges in the Development of Novel Inhalants Mediated by the Proton-Sensing Receptor OGR1 in Airway Inflammation"}]}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360011143736398080","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"THE CARDIAC FIBROBLAST: Therapeutic Target in Myocardial Remodeling and Failure"}]},{"@id":"https://cir.nii.ac.jp/crid/1360011144224105472","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"FasL expression in cardiomyocytes activates the ERK1/2 pathway, leading to dilated cardiomyopathy and advanced heart 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Controls the Developmental Loss in Ability of Axons to Regenerate"}]},{"@id":"https://cir.nii.ac.jp/crid/1360298336539382144","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Role of peripheral myelin protein 22 in chronic exercise‐induced interactions of muscle and bone in mice"}]},{"@id":"https://cir.nii.ac.jp/crid/1360567180121414784","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Ameloblastin attenuates RANKL‐mediated osteoclastogenesis by suppressing activation of nuclear factor of activated T‐cell cytoplasmic 1 (NFATc1)"}]},{"@id":"https://cir.nii.ac.jp/crid/1360567186730428672","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Nitrogen-containing bisphosphonates inhibit RANKL- and M-CSF-induced osteoclast formation through the inhibition of ERK1/2 and Akt activation"}]},{"@id":"https://cir.nii.ac.jp/crid/1360574093736024832","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"An ATF/CREB-binding site is essential for cell-specific and inducible transcription of the murine MIP-1β cytokine gene"}]},{"@id":"https://cir.nii.ac.jp/crid/1360574093756576896","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"TNF -induced GM-CSF release from human airway smooth muscle cells depends on activation of an ET-1 autoregulatory positive feedback mechanism"}]},{"@id":"https://cir.nii.ac.jp/crid/1360574093924343424","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Rapid Effects of Retinoic Acid on CREB and ERK Phosphorylation in Neuronal Cells"}]},{"@id":"https://cir.nii.ac.jp/crid/1360574095132674304","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Angiotensin II Plays a Critical Role in Alcohol-Induced Cardiac Nitrative Damage, Cell Death, Remodeling, and Cardiomyopathy in a Protein Kinase C/Nicotinamide Adenine Dinucleotide Phosphate Oxidase–Dependent Manner"}]},{"@id":"https://cir.nii.ac.jp/crid/1360574095850023040","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Epac1 is upregulated during neointima formation and promotes vascular smooth muscle cell migration"}]},{"@id":"https://cir.nii.ac.jp/crid/1360574095899807232","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"p116Rip Decreases Myosin II Phosphorylation by Activating Myosin Light Chain Phosphatase and by Inactivating RhoA"}]},{"@id":"https://cir.nii.ac.jp/crid/1360574096249798016","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Deletion of Angiotensin-Converting Enzyme 2 Accelerates Pressure Overload-Induced Cardiac Dysfunction by Increasing Local Angiotensin II"}]},{"@id":"https://cir.nii.ac.jp/crid/1360574096361019008","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Structure, evolution, and biology of the MUC4 mucin"}]},{"@id":"https://cir.nii.ac.jp/crid/1360846643191463552","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"cAMP and Epac in the regulation of tissue fibrosis"}]},{"@id":"https://cir.nii.ac.jp/crid/1360848656931915648","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Ameloblastin and enamelin prevent osteoclast formation by suppressing RANKL expression via MAPK signaling pathway"}]},{"@id":"https://cir.nii.ac.jp/crid/1360855569874857216","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Rit-mediated Stress Resistance Involves a p38-Mitogen- and Stress-activated Protein Kinase 1 (MSK1)-dependent cAMP Response Element-binding Protein (CREB) Activation Cascade"}]},{"@id":"https://cir.nii.ac.jp/crid/1360855570356216576","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"The role of cAMP and its downstream targets in neurite growth in the adult nervous system"}]},{"@id":"https://cir.nii.ac.jp/crid/1360855570780498432","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"CREB Mediates UTP-Directed Arterial Smooth Muscle Cell Migration and Expression of the Chemotactic Protein Osteopontin via Its Interaction with Activator Protein-1 Sites"}]},{"@id":"https://cir.nii.ac.jp/crid/1360855571217131392","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"IL-1β Upregulates StAR and Progesterone Production Through the ERK1/2- and p38-Mediated CREB Signaling Pathways in Human Granulosa-Lutein Cells"}]},{"@id":"https://cir.nii.ac.jp/crid/1360855571412836608","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"The intracellular renin–angiotensin system: implications in cardiovascular remodeling"}]},{"@id":"https://cir.nii.ac.jp/crid/1360855571434371840","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Agonist-induced changes in the phosphorylation of the myosin- binding subunit of myosin light chain phosphatase and CPI17, two regulatory factors of myosin light chain phosphatase, in smooth muscle"}]},{"@id":"https://cir.nii.ac.jp/crid/1360861294958551808","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Protein kinase C mediates activation of nuclear cAMP response element-binding protein (CREB) in B lymphocytes stimulated through surface Ig."}]},{"@id":"https://cir.nii.ac.jp/crid/1361137044228641408","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Involvement of p38 Mitogen-activated Protein Kinase Signaling Pathway in Osteoclastogenesis Mediated by Receptor Activator of NF-κB Ligand (RANKL)"}]},{"@id":"https://cir.nii.ac.jp/crid/1361137044334626688","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"CREB Phosphorylation and Dephosphorylation: A Ca2+- and Stimulus Duration–Dependent Switch for Hippocampal Gene Expression"}]},{"@id":"https://cir.nii.ac.jp/crid/1361137044651443968","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"The Role of Specific Mitogen-Activated Protein Kinase Signaling Cascades in the Regulation of Steroidogenesis"}]},{"@id":"https://cir.nii.ac.jp/crid/1361137045489692032","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Novel Cytoplasmic Proteins of Nontypeable 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