Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/11647
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dc.contributor.authorHuynh, Nhien
dc.contributor.authorYim, Mildreden
dc.contributor.authorChernoff, Jonathanen
dc.contributor.authorShulkes, Arthuren
dc.contributor.authorBaldwin, Graham Sen
dc.contributor.authorHe, Hongen
dc.date.accessioned2015-05-16T01:15:51Z
dc.date.available2015-05-16T01:15:51Z
dc.date.issued2013-01-10en
dc.identifier.citationAmerican Journal of Physiology. Gastrointestinal and Liver Physiology 2013; 304(6): G561-7en
dc.identifier.govdoc23306081en
dc.identifier.otherPUBMEDen
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/11647en
dc.description.abstractGastrins, including amidated (Gamide) and glycine-extended (Ggly) forms, function as growth factors for the gastrointestinal mucosa. The p-21-activated kinase 1 (PAK1) plays important roles in growth factor signaling networks that control cell motility, proliferation, differentiation, and transformation. PAK1, activated by both Gamide and Ggly, mediates gastrin-stimulated proliferation and migration, and activation of β-catenin, in gastric epithelial cells. The aim of this study was to investigate the role of PAK1 in the regulation by gastrin of proliferation in the normal colorectal mucosa in vivo. Mucosal proliferation was measured in PAK1 knockout (PAK1 KO) mice by immunohistochemistry. The expression of phosphorylated and unphosphorylated forms of the signaling molecules PAK1, extracellular signal-regulated kinase (ERK), and protein kinase B (AKT), and the expression of β-catenin and its downstream targets c-Myc and cyclin D1, were measured in gastrin knockout (Gas KO) and PAK1 KO mice by Western blotting. The expression and activation of PAK1 are decreased in Gas KO mice, and these decreases are associated with reduced activation of ERK, AKT, and β-catenin. Proliferation in the colorectal mucosa of PAK1 KO mice is reduced, and the reduction is associated with reduced activation of ERK, AKT, and β-catenin. In compensation, antral gastrin mRNA and serum gastrin concentrations are increased in PAK1 KO mice. These results indicate that PAK1 mediates the stimulation of colorectal proliferation by gastrins via multiple signaling pathways involving activation of ERK, AKT, and β-catenin.en
dc.language.isoenen
dc.subject.otherAnimalsen
dc.subject.otherCell Differentiation.physiologyen
dc.subject.otherCell Movement.physiologyen
dc.subject.otherCell Proliferationen
dc.subject.otherCell Survival.physiologyen
dc.subject.otherColon.pathologyen
dc.subject.otherCyclin D1.metabolismen
dc.subject.otherDown-Regulationen
dc.subject.otherExtracellular Signal-Regulated MAP Kinases.metabolismen
dc.subject.otherGastrins.metabolismen
dc.subject.otherImmunohistochemistryen
dc.subject.otherIntestinal Mucosa.metabolism.pathologyen
dc.subject.otherMiceen
dc.subject.otherMice, Inbred C57BLen
dc.subject.otherMice, Knockouten
dc.subject.otherProto-Oncogene Proteins c-akt.metabolismen
dc.subject.otherRectum.pathologyen
dc.subject.otherSignal Transduction.physiologyen
dc.subject.otherbeta Catenin.metabolismen
dc.subject.otherp21-Activated Kinases.metabolismen
dc.titlep-21-Activated kinase 1 mediates gastrin-stimulated proliferation in the colorectal mucosa via multiple signaling pathways.en
dc.typeJournal Articleen
dc.identifier.journaltitleAmerican journal of physiology. Gastrointestinal and liver physiologyen
dc.identifier.affiliationDepartment of Surgery, University of Melbourne, Austin Health, Victoria, Australiaen
dc.identifier.doi10.1152/ajpgi.00218.2012en
dc.description.pagesG561-7en
dc.relation.urlhttps://pubmed.ncbi.nlm.nih.gov/23306081en
dc.type.austinJournal Articleen
local.name.researcherHe, Hong
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.fulltextNo Fulltext-
item.grantfulltextnone-
item.languageiso639-1en-
item.openairetypeJournal Article-
crisitem.author.deptSurgery (University of Melbourne)-
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