Related Experiment Video

Updated: Aug 29, 2026

Direct Imaging of ER Calcium with Targeted-Esterase Induced Dye Loading (TED)
09:32

Direct Imaging of ER Calcium with Targeted-Esterase Induced Dye Loading (TED)

Published on: May 7, 2013

Calcium-sensing receptor-mediated ERK1/2 activation requires Galphai2 coupling and dynamin-independent receptor

Deborah M Holstein1, Kelly A Berg, L M Fredrik Leeb-Lundberg

  • 1Department of Biochemistry, University of Texas Health Science Center at San Antonio, 78229-3900, USA.

The Journal of Biological Chemistry
|January 1, 2004
PubMed

Insights

The calcium-sensing receptor (CaR) activates ERK1/2 via distinct pathways depending on the agonist. NPS R-467/CaCl(2) activates ERK1/2 without desensitization, while Ca(2+) alone shows rapid desensitization and recovery.

Area of Science:

  • Cellular signaling
  • Molecular biology
  • Biochemistry

Background:

  • The calcium-sensing receptor (CaR) is known to activate MAP kinase (ERK1/2).
  • Understanding CaR signaling pathways is crucial for deciphering cellular responses.

Purpose of the Study:

  • To investigate the distinct pathways of CaR-mediated ERK1/2 activation by different stimuli.
  • To elucidate the roles of internalization, dynamin, beta-arrestin, and G proteins in CaR signaling.

Main Methods:

  • Utilized human embryonic kidney cells expressing the human CaR (HEK-hCaR).
  • Stimulated cells with Ca(2+) and the CaR agonist NPS R-467.
  • Investigated CaR internalization using concanavalin A.
  • Assessed the involvement of dynamin and beta-arrestin using dominant-negative mutants.
  • Examined G protein involvement with pertussis toxin and G protein mutants.

Main Results:

  • NPS R-467/CaCl(2) and 4 mm Ca(2+) differentially activated ERK1/2 with distinct kinetics and desensitization patterns.
  • CaR internalization was essential for NPS R-467/CaCl(2)-mediated ERK1/2 activation but not for initial 4 mm Ca(2+) activation.
  • ERK1/2 activation occurred via a dynamin-independent pathway.
  • Galpha(i2) mediated the pertussis toxin-sensitive component of 4 mm Ca(2+)-induced ERK1/2 activation.

Conclusions:

  • CaR activates ERK1/2 through distinguishable pathways modulated by specific agonists and extracellular calcium concentrations.
  • These distinct pathways may differentially regulate cell differentiation and proliferation.
  • Findings provide insights into the complex regulation of CaR signaling.

More Related Videos

Monitoring ER/SR Calcium Release with the Targeted Ca2+ Sensor CatchER+12:30

Monitoring ER/SR Calcium Release with the Targeted Ca2+ Sensor CatchER+

Published on: May 19, 2017

Monitoring Endoplasmic Reticulum Calcium Homeostasis Using a Gaussia Luciferase SERCaMP08:41

Monitoring Endoplasmic Reticulum Calcium Homeostasis Using a Gaussia Luciferase SERCaMP

Published on: September 6, 2015

Related Concept Videos

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,...
Feedback Regulation of Calcium Concentration01:27

Feedback Regulation of Calcium Concentration

Calcium is an essential signaling molecule required for various cellular functions. Calcium pumps and ion channels on cell and organellar membranes, such as those on the endoplasmic reticulum (ER), regulate calcium concentrations inside the cell. They remain closed, keeping the cytosolic calcium levels low at a resting state.
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and produces two-second...
Amplifying Signals via Second Messengers01:15

Amplifying Signals via Second Messengers

Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...
What are Second Messengers?02:04

What are Second Messengers?

Because many receptor binding ligands are hydrophilic, they do not cross the cell membrane and thus their message must be relayed to a second messenger on the inside. There are several second messenger pathways, each with their own way of relaying information. G-protein coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol path is active when the receptor induces phospholipase C to hydrolyze the phospholipid,...
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 the...