Source:http://linkedlifedata.com/resource/pubmed/id/11018757
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
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| pubmed:dateCreated |
2000-11-9
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| pubmed:abstractText |
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.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CDKN1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Calcitonin,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclins,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Calcitonin
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| pubmed:status |
MEDLINE
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| pubmed:month |
Oct
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| pubmed:issn |
0022-0795
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
167
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
93-105
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:11018757-Binding, Competitive,
pubmed-meshheading:11018757-Calcitonin,
pubmed-meshheading:11018757-Calcium,
pubmed-meshheading:11018757-Cell Culture Techniques,
pubmed-meshheading:11018757-Cell Cycle,
pubmed-meshheading:11018757-Cell Division,
pubmed-meshheading:11018757-Cyclic AMP,
pubmed-meshheading:11018757-Cyclin-Dependent Kinase Inhibitor p21,
pubmed-meshheading:11018757-Cyclins,
pubmed-meshheading:11018757-Dose-Response Relationship, Drug,
pubmed-meshheading:11018757-Humans,
pubmed-meshheading:11018757-Hydrogen-Ion Concentration,
pubmed-meshheading:11018757-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:11018757-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:11018757-Mitogen-Activated Protein Kinases,
pubmed-meshheading:11018757-Protein Isoforms,
pubmed-meshheading:11018757-Receptors, Calcitonin,
pubmed-meshheading:11018757-Signal Transduction
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| pubmed:year |
2000
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| pubmed:articleTitle |
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.
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| pubmed:affiliation |
Department of Orthopaedics and Trauma, University of Adelaide, The Royal Adelaide Hospital, Adelaide 5000, South Australia, Australia.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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