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https://hdl.handle.net/2440/6795
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dc.contributor.author | Raggatt, L. | - |
dc.contributor.author | Evdokiou, A. | - |
dc.contributor.author | Findlay, D. | - |
dc.date.issued | 2000 | - |
dc.identifier.citation | Journal of Endocrinology, 2000; 167(1):93-105 | - |
dc.identifier.issn | 0022-0795 | - |
dc.identifier.issn | 1479-6805 | - |
dc.identifier.uri | http://hdl.handle.net/2440/6795 | - |
dc.description.abstract | Recently we reported that calcitonin (CT) induces growth arrest at the G2 stage of the cell cycle in HEK-293 cell lines expressing the most abundant, insert-negative, isoform of the human CT receptor (insert -ve hCTR). The present study investigates the involvement of the MAPK signalling pathway in the anti-proliferative actions of CT and compares the activity of an isoform of the hCTR that contains a 16 amino acid insert in the first putative intracellular loop (insert +ve hCTR). Comparison of HEK-293 cells stably transfected with the insert -ve or the insert +ve hCTR, showed that accumulation of cAMP and intracellular free calcium in response to CT were specific for the insert -ve receptor isoform. However, a novel acidification of the extracellular medium was mediated by both isoforms. Treatment with CT of cells expressing the insert -ve hCTR, caused a decrease in cell growth associated with an induction of p21(WAF1/CIP1). Analysis by fluorescence-activated cell scanning showed that growth inhibition was associated with an accumulation of cells in G2. CT treatment of cells expressing the insert -ve, but not insert +ve hCTR, induced the phosphorylation of Erk1/2 MAPK, which persisted for at least 72 h. Treatment of cells expressing the insert -ve hCTR with the MAPK kinase (MEK) inhibitor, PD-98059, inhibited the phosphorylation of Erk1/2 and abrogated the growth inhibitory effects of salmon CT, the accumulation of cells in G2, and the associated induction of p21(WAF1/CIP1). These data suggest that activation of Erk1/2 are downstream effectors of the insert -ve hCTR in modulating cell cycle progression. | - |
dc.language.iso | en | - |
dc.publisher | Soc Endocrinology | - |
dc.source.uri | http://dx.doi.org/10.1677/joe.0.1670093 | - |
dc.subject | Humans | - |
dc.subject | Calcium | - |
dc.subject | Calcitonin | - |
dc.subject | Mitogen-Activated Protein Kinases | - |
dc.subject | Mitogen-Activated Protein Kinase 1 | - |
dc.subject | Mitogen-Activated Protein Kinase 3 | - |
dc.subject | Cyclins | - |
dc.subject | Receptors, Calcitonin | - |
dc.subject | Protein Isoforms | - |
dc.subject | Cyclic AMP | - |
dc.subject | Cell Culture Techniques | - |
dc.subject | Signal Transduction | - |
dc.subject | Cell Cycle | - |
dc.subject | Cell Division | - |
dc.subject | Binding, Competitive | - |
dc.subject | Dose-Response Relationship, Drug | - |
dc.subject | Hydrogen-Ion Concentration | - |
dc.subject | Cyclin-Dependent Kinase Inhibitor p21 | - |
dc.title | Sustained activation of Erk1/2 MAPK and cell growth suppression by the insert-negative, but not the insert-positive isoform of the human calcitonin receptor | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1677/joe.0.1670093 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Evdokiou, A. [0000-0001-8321-9806] | - |
Appears in Collections: | Aurora harvest 5 Orthopaedics and Trauma publications |
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