Related Experiment Video

Updated: Aug 21, 2026

Assaying Protein Kinase Activity with Radiolabeled ATP
08:05

Assaying Protein Kinase Activity with Radiolabeled ATP

Published on: May 26, 2017

SNT-2 interacts with ERK2 and negatively regulates ERK2 signaling in response to EGF stimulation

Lin Huang1, Noriko Gotoh, Shengliang Zhang

  • 1Department of Molecular Cellular Oncology and Microbiology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yujima, Bunkyo-ku, Tokyo 113-8510, Japan.

Biochemical and Biophysical Research Communications
|October 16, 2004
PubMed

Insights

Suc1-binding neurotrophic target-2 (SNT-2) directly binds to ERK2, a key signaling protein. This interaction negatively regulates EGF-stimulated ERK2 activity, impacting cellular responses.

Area of Science:

  • Cellular signaling pathways
  • Molecular biology
  • Signal transduction

Background:

  • Cellular responses to fibroblast growth factors and neurotrophins are regulated by docking proteins SNT-1/FRS2alpha and SNT-2/FRS2beta.
  • ERK1/2 (extracellular signal-regulated kinases 1/2) are crucial mitogen-activated protein kinases involved in diverse cellular activities.

Purpose of the Study:

  • To investigate the interaction between SNT-2 and ERK2.
  • To elucidate the role of SNT-2 in regulating EGF-stimulated ERK signaling.

Main Methods:

  • Analysis of SNT-2 tyrosine phosphorylation upon EGF stimulation.
  • Co-immunoprecipitation assays to detect SNT-2 and ERK2 complex formation.
  • Examination of ERK2 phosphorylation and nuclear accumulation in the presence of wild-type and mutant SNT-2.

Main Results:

  • SNT-2 does not undergo significant tyrosine phosphorylation in response to EGF but forms a complex with ERK2.
  • Complex formation between SNT-2 and ERK2 is enhanced by EGF stimulation, mediated by amino acid residues 186-252 of SNT-2.
  • SNT-2 negatively regulates EGF-induced ERK2 phosphorylation and delays its nuclear accumulation.

Conclusions:

  • SNT-2 directly binds to ERK2, suggesting a novel regulatory mechanism.
  • SNT-2 acts as a negative regulator of EGF-stimulated ERK2 signaling through direct physical interaction.
  • These findings highlight SNT-2's role in modulating cellular responses to growth factor stimulation.

More Related Videos

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

Spatial and Temporal Analysis of Active ERK in the C. elegans Germline08:40

Spatial and Temporal Analysis of Active ERK in the C. elegans Germline

Published on: November 29, 2016

Related Concept Videos

Enzyme-linked Receptors01:00

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
Receptor Tyrosine Kinases01:26

Receptor Tyrosine Kinases

Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
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...
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...