| First Author | Rey O | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 2 | Pages | 1158-67 |
| PubMed ID | 22094462 | Mgi Jnum | J:179672 |
| Mgi Id | MGI:5302881 | Doi | 10.1074/jbc.M111.274589 |
| Citation | Rey O, et al. (2012) Negative Cross-talk between Calcium-sensing Receptor and beta-Catenin Signaling Systems in Colonic Epithelium. J Biol Chem 287(2):1158-67 |
| abstractText | Here, we examined the role of the extracellular Ca(2+)-sensing receptor (CaSR) in the control of colonic epithelial cell proliferation in vivo and changes in beta-catenin triggered by CaSR stimulation in human colonic epithelial cells in vitro. The in vivo studies, using a novel Casr intestinal-specific knock-out mouse, indicate that the genetic ablation of the Casr leads to hyperproliferation of colonic epithelial cells, expansion of the proliferative zone, changes in crypt structure, and enhanced beta-catenin nuclear localization. The in vitro results indicate that stimulation of the CaSR, by Ca(2+) or by the calcimimetic R-568, produced a striking and time-dependent decrease in the phosphorylation of beta-catenin at Ser-552 and Ser-675, two amino acid residues that promote beta-catenin transcriptional activity. The reduced phosphorylation of beta-catenin coincided with a decline in its nuclear localization and a marked redistribution to the plasma membrane. Furthermore, CaSR stimulation promoted a down-regulation of beta-catenin-mediated transcriptional activation. These studies demonstrate that signaling pathways emanating from the CaSR control colonic epithelial cell proliferation in vivo and suggest that the mechanism involves regulation of beta-catenin phosphorylation. |
