Related Experiment Video

Updated: Mar 12, 2026

Targeting Cysteine Thiols for in Vitro Site-specific Glycosylation of Recombinant Proteins
11:25

Targeting Cysteine Thiols for in Vitro Site-specific Glycosylation of Recombinant Proteins

Published on: October 4, 2017

7.2K

Phosphocysteine in the PRL-CNNM pathway mediates magnesium homeostasis

Irina Gulerez1, Yosuke Funato2, Howie Wu1

  • 1Department of Biochemistry and Groupe de recherche axé sur la structure des protéines, McGill University, Montreal, Quebec, Canada.

EMBO Reports
|November 19, 2016
PubMed

Insights

Phosphatases of regenerating liver (PRLs) interact with CNNM transporters, regulating Mg2+ transport. This interaction is controlled by phosphocysteine, a novel regulatory modification impacting cancer progression.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Phosphatases of regenerating liver (PRLs) are overexpressed in cancers and linked to poor survival.
  • PRLs' weak enzymatic activity hinders understanding of their mechanism and therapeutic potential.
  • PRLs interact with CNNM ion transporters, inhibiting Mg2+ transport crucial for tumor progression.

Purpose of the Study:

  • To elucidate the regulatory mechanism of PRL-CNNM complex formation.
  • To investigate the role of phosphocysteine in PRL function and Mg2+ transport regulation.
  • To determine the structural basis of the PRL-CNNM interaction.

Main Methods:

  • Investigated endogenous phosphocysteine formation in PRLs.
  • Assessed the impact of Mg2+ levels on phosphocysteine.
  • Utilized cell-based assays to study Mg2+ efflux regulation.
  • Determined the crystal structure of the PRL2-CNNM3 complex.

Main Results:

  • Identified endogenous phosphocysteine in the PRL catalytic site, regulated by Mg2+ levels.
  • Demonstrated that phosphocysteine blocks PRL binding to CNNM transporters.
  • Showed that mutations disrupting PRL-CNNM interaction impair Mg2+ efflux regulation.
  • Resolved the crystal structure of the PRL2-CNNM3 complex, revealing interaction details.

Conclusions:

  • Phosphocysteine is a novel regulatory modification controlling PRL-CNNM interactions.
  • This phosphocysteine-mediated regulation impacts Mg2+ transport and cellular processes.
  • Findings offer new insights into protein phosphatase signaling and potential therapeutic strategies for cancer.
Keywords:
X‐ray crystallographycysteinemagnesiumphosphatasephosphorylation

More Related Videos

Fluorescence-Based Measurements of Phosphatidylserine/Phosphatidylinositol 4-Phosphate Exchange Between Membranes08:49

Fluorescence-Based Measurements of Phosphatidylserine/Phosphatidylinositol 4-Phosphate Exchange Between Membranes

Published on: March 14, 2021

4.7K
Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons10:50

Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons

Published on: April 24, 2021

1.4K

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,...
6.9K
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...
15.5K
pH Regulation in Cells01:28

pH Regulation in Cells

pH plays a critical role in maintaining normal cellular activities. It helps maintain the structure and function of various proteins, dictates the charge on cellular membranes, and is crucial for metabolic reactions inside the cell. Moreover, cells use the energy from the proton motive force to generate ATP.
Cytosolic pH
Under physiological conditions, the cytosolic pH is slightly more acidic than the extracellular pH. However, cells must prevent further acidification of their cytosol to...
8.0K
Ligand-Gated Ion Channel Receptor: Gating Mechanism01:30

Ligand-Gated Ion Channel Receptor: Gating Mechanism

Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
4.5K
Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
10.4K
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
15.4K