Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/6795
Citations | ||
Scopus | Web of ScienceĀ® | Altmetric |
---|---|---|
?
|
?
|
Type: | Journal article |
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 |
Author: | Raggatt, L. Evdokiou, A. Findlay, D. |
Citation: | Journal of Endocrinology, 2000; 167(1):93-105 |
Publisher: | Soc Endocrinology |
Issue Date: | 2000 |
ISSN: | 0022-0795 1479-6805 |
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. |
Keywords: | Humans Calcium Calcitonin Mitogen-Activated Protein Kinases Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Cyclins Receptors, Calcitonin Protein Isoforms Cyclic AMP Cell Culture Techniques Signal Transduction Cell Cycle Cell Division Binding, Competitive Dose-Response Relationship, Drug Hydrogen-Ion Concentration Cyclin-Dependent Kinase Inhibitor p21 |
DOI: | 10.1677/joe.0.1670093 |
Published version: | http://dx.doi.org/10.1677/joe.0.1670093 |
Appears in Collections: | Aurora harvest 5 Orthopaedics and Trauma publications |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.