Related Experiment Video

Updated: May 11, 2026

Assaying Protein Kinase Activity with Radiolabeled ATP
08:05

Assaying Protein Kinase Activity with Radiolabeled ATP

Published on: May 26, 2017

Phosphoproteome dynamics reveal novel ERK1/2 MAP kinase substrates with broad spectrum of functions

Mathieu Courcelles1, Christophe Frémin, Laure Voisin

  • 1Institute for Research in Immunology and Cancer, Université de Montréal, Montreal, Quebec, Canada.

Molecular Systems Biology
|May 29, 2013
PubMed

Insights

Researchers identified new targets of the ERK1/2 MAP kinase pathway using phosphoproteomics. This reveals ERK1/2

Area of Science:

  • Cellular signaling
  • Molecular biology
  • Biochemistry

Background:

  • The ERK1/2 MAP kinase pathway regulates critical physiological processes.
  • Dysregulation of ERK1/2 is linked to human diseases and developmental disorders.
  • A complete understanding of ERK1/2 substrates and regulatory mechanisms is currently lacking.

Purpose of the Study:

  • To identify novel substrates of the ERK1/2 pathway.
  • To elucidate the biochemical mechanisms regulated by ERK1/2.
  • To expand the known cellular functions controlled by ERK1/2 kinases.

Main Methods:

  • Large-scale quantitative phosphoproteomics was employed to identify potential substrates.
  • Bioinformatics analyses were used to analyze phosphorylation signatures and kinetic profiles.
  • Epithelial cells were utilized for the experimental investigation.

Main Results:

  • A total of 7936 phosphorylation sites in 1861 proteins were identified.
  • 155 proteins were classified as candidate ERK1/2 substrates, including 128 novel targets.
  • Newly identified substrates participate in transcriptional regulation, chromatin remodeling, RNA splicing, cytoskeleton dynamics, and cell signaling.

Conclusions:

  • The study significantly expands the known repertoire of ERK1/2 substrates.
  • ERK1/2 kinases regulate a wide array of cellular functions.
  • Phosphorylation of the transcriptional regulator JunB by ERK1/2 enhances its DNA-binding and transcriptional activity.

More Related Videos

Identification of Kinase-substrate Pairs Using High Throughput Screening11:13

Identification of Kinase-substrate Pairs Using High Throughput Screening

Published on: August 29, 2015

A Mass Spectrometry-Based Approach to Identify Phosphoprotein Phosphatases and their Interactors10:17

A Mass Spectrometry-Based Approach to Identify Phosphoprotein Phosphatases and their Interactors

Published on: April 29, 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...
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...
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...
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...
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...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...