Related Experiment Video

Updated: May 5, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

13.1K

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

Diana Organista-Juárez1, Jorge Carretero-Ortega, Onasis Vicente-Fermín

  • 1Department of Cell Biology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Apartado postal 14-740, México, D.F. 07000, Mexico.

IUBMB Life
|November 26, 2013
PubMed

Insights

The calcium-sensing receptor (CaSR) inhibits transforming growth factor-beta (TGF-β) signaling by reducing Smad2 phosphorylation and degradation. This CaSR-mediated TGF-β inhibition is linked to Rab11-dependent receptor trafficking.

Area of Science:

  • Cell Biology
  • Molecular Signaling
  • Gastroenterology

Background:

  • The calcium-sensing receptor (CaSR) primarily regulates extracellular calcium homeostasis.
  • CaSR also influences cellular functions like proliferation and migration through signaling cross-talk.
  • Transforming growth factor-beta (TGF-β) signaling plays a critical role in various cellular processes.

Purpose of the Study:

  • To investigate the interaction between CaSR and TGF-β signaling pathways.
  • To determine if CaSR modulates TGF-β signaling in non-homeostatic contexts.
  • To elucidate the molecular mechanisms underlying CaSR's effect on TGF-β signaling.

Main Methods:

  • Experiments were conducted in hepatic C9 cells and transfected HEK293 cells.
  • Assessed TGF-β-dependent Smad2 phosphorylation and proteasomal degradation.
  • Investigated the role of CaSR trafficking and its carboxyl-terminal tail in the signaling modulation.

Main Results:

  • Wild-type CaSR significantly attenuates TGF-β signaling, evidenced by reduced Smad2 phosphorylation and increased degradation.
  • An inactivating CaSR mutant failed to inhibit TGF-β signaling in response to extracellular calcium.
  • CaSR-mediated inhibition of TGF-β signaling is dependent on Rab11-mediated receptor trafficking.

Conclusions:

  • CaSR inhibits TGF-β signaling, impacting TGF-β-dependent cellular responses.
  • Extracellular calcium levels, through CaSR, can modulate TGF-β pathway activity.
  • CaSR's carboxyl-terminal tail and Rab11-dependent trafficking are crucial for this inhibitory cross-talk.
Keywords:
GPCRSmadTGF-β; cell signalingcalcium sensing receptortrafficking

More Related Videos

Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay11:38

Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay

Published on: September 14, 2021

2.4K
Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling07:49

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling

Published on: August 3, 2018

10.1K

Related Concept Videos

TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.2K
Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
5.0K
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.0K
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
15.3K
Hormones and Bone Tissue01:17

Hormones and Bone Tissue

The endocrine system produces and secretes hormones, which interact with the skeletal system. These hormones control bone growth, maintain bone once it is formed, and remodel it.
Hormones That Influence Osteoblasts and/or Maintain the Matrix
Several hormones are necessary for controlling bone growth and maintaining the bone matrix. The pituitary gland secretes growth hormone (GH), which, as its name implies, controls bone growth. This happens in several ways: first, it triggers chondrocyte...
3.5K
Skeleton and Calcium Homeostasis01:21

Skeleton and Calcium Homeostasis

Calcium is not only the most abundant mineral in bone but also the most abundant mineral in the human body. Calcium ions are needed for bone mineralization, tooth health, heart rate regulation and strength of contraction, blood coagulation, the contraction of smooth and skeletal muscle cells, and the regulation of nerve impulse conduction. The average calcium level in the blood is about 10 mg/dL. When the body cannot maintain this level, a person will experience hypo or hypercalcemia.
8.5K