Related Experiment Video

Updated: May 29, 2026

Assaying Protein Kinase Activity with Radiolabeled ATP
08:05

Assaying Protein Kinase Activity with Radiolabeled ATP

Published on: May 26, 2017

Mxi2 sustains ERK1/2 phosphorylation in the nucleus by preventing ERK1/2 binding to phosphatases

Berta Casar1, Javier Rodríguez, Gilad Gibor

  • 1Instituto de Biomedicina y Biotecnología de Cantabria, Consejo Superior de Investigaciones Científicas - IDICAN - Universidad de Cantabria, Santander 39011, Cantabria, Spain.

The Biochemical Journal
|September 29, 2011
PubMed

Insights

Mxi2, a p38α splice isoform, spatially regulates ERK1/2 (extracellular-signal-regulated kinase 1/2) signaling. It enhances nuclear ERK1/2 activity by preventing dephosphorylation and can potentiate cytoplasmic ERK1/2 functions when relocated.

Area of Science:

  • Cellular signaling and molecular biology
  • Mitogen-activated protein kinase (MAPK) pathways
  • Protein regulation and localization

Background:

  • ERK1/2 (extracellular-signal-regulated kinase 1/2) MAPKs are crucial signaling molecules regulated by their cellular microenvironment.
  • Mxi2, a p38α splice isoform, interacts with ERK1/2, promoting nuclear translocation and sustained phosphorylation.
  • The precise molecular mechanisms by which Mxi2 influences ERK1/2 activity remain largely undefined.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying Mxi2-mediated spatial regulation of ERK1/2 signaling.
  • To investigate how Mxi2 influences the interaction of ERK1/2 with phosphatases in different cellular compartments.
  • To explore the functional consequences of altering Mxi2's subcellular localization on ERK1/2 activity.

Main Methods:

  • Investigated the binding interactions between Mxi2, ERK1/2, and phosphatases in nuclear and cytoplasmic compartments.
  • Utilized techniques to assess ERK1/2 phosphorylation levels in response to Mxi2.
  • Experimentally tethered Mxi2 to the cytoplasm to study its effects on ERK1/2 signaling kinetics.

Main Results:

  • Mxi2 selectively inhibits nuclear phosphatases from dephosphorylating ERK1/2, thereby enhancing nuclear ERK1/2 signaling.
  • Mxi2 does not prevent cytoplasmic phosphatases from interacting with ERK1/2.
  • Artificially sequestering Mxi2 in the cytoplasm potentiates ERK1/2 functions within this compartment by preventing inactivation.

Conclusions:

  • Mxi2 acts as a critical spatial regulator of ERK1/2 signaling, controlling its activity in distinct cellular compartments.
  • Mxi2's mechanism involves the selective blockade of nuclear ERK1/2 dephosphorylation.
  • The balance between nuclear and cytoplasmic ERK1/2 signaling is significantly influenced by Mxi2 localization and function.

More Related Videos

Subcellular Fractionation for ERK Activation Upon Mitochondrial-derived Peptide Treatment07:55

Subcellular Fractionation for ERK Activation Upon Mitochondrial-derived Peptide Treatment

Published on: September 25, 2017

Study of the Functions and Activities of Neuronal K-Cl Co-Transporter KCC2 Using Western Blotting10:08

Study of the Functions and Activities of Neuronal K-Cl Co-Transporter KCC2 Using Western Blotting

Published on: December 9, 2022

Related Concept Videos

MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
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,...
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...