Please use this identifier to cite or link to this item:
|Scopus||Web of Science®||Altmetric|
|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|
|Citation:||Journal of Endocrinology, 2000; 167(1):93-105|
|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|
|Appears in Collections:||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.