Calcium-sensing receptor inhibits TGF-β-signaling by decreasing Smad2 phosphorylation

Organista-Juárez, D; Carretero-Ortega, J; Vicente-Fermín, O; Vázquez-Victorio, G; Sosa-Garrocho, M; Vázquez-Prado, J; Macías-Silva, M; Reyes-Cruz, G

HERO ID

2900057

Reference Type

Journal Article

Year

2013

Language

English

PMID

24273150

HERO ID 2900057
In Press No
Year 2013
Title Calcium-sensing receptor inhibits TGF-β-signaling by decreasing Smad2 phosphorylation
Authors Organista-Juárez, D; Carretero-Ortega, J; Vicente-Fermín, O; Vázquez-Victorio, G; Sosa-Garrocho, M; Vázquez-Prado, J; Macías-Silva, M; Reyes-Cruz, G
Journal IUBMB Life
Volume 65
Issue 12
Page Numbers 1035-1042
Abstract Calcium-sensing receptor (CaSR) contributes to maintain homeostatic levels of extracellular calcium. In addition, CaSR controls other cellular activities such as proliferation and migration, particularly in cells not related to extracellular calcium homeostasis, potentially by cross-talking with parallel signaling pathways. Here we report that CaSR attenuates transforming growth factor-β (TGF-β)-signaling in hepatic C9 cells and in transfected HEK293 cells. Wild type CaSR interferes with TGF-β-dependent Smad2 phosphorylation and induces its proteasomal degradation, resulting in a decrease of TGF-β-dependent transcriptional activity, whereas an inactivating CaSR mutant does not transduce an inhibitory effect of extracellular calcium on TGF-β signaling. Attenuation of TGF-β signaling in response to extracellular calcium is linked to Rab11-dependent CaSR-trafficking with the intervention of CaSR carboxyl-terminal tail. Our data suggest that CaSR might regulate TGF-β-dependent cellular responses mediated by TGF-β signaling inhibition.
Doi 10.1002/iub.1232
Pmid 24273150
Is Certified Translation No
Dupe Override No
Is Public Yes
Language Text English