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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...
Directionality of Nuclear Transport01:42

Directionality of Nuclear Transport

Ras-related nuclear protein or Ran is a small G protein that cycles between its GTP and GDP bound states. Ran specific regulators, a Ran GTPase Activating Protein or RanGAP present in the cytosol and a Ran guanine nucleotide exchange factor or RanGEF present inside the nucleus regulate GTP/GDP exchange. A high concentration of GTP inside the cells, in addition to this asymmetric distribution of  Ran-specific regulators, leads to a higher RanGTP concentration inside the nucleus. This...
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...
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...
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
The Two-State Receptor Model01:29

The Two-State Receptor Model

The two-state receptor model explains a drug's interaction with receptors, such as G protein-coupled receptors and ligand-gated ion channels, to induce or inhibit a biological response. When no natural ligands are present, a receptor exists in an equilibrium of inactive (Ri) and active (Ra) conformations. The inactive form does not produce a response, while the active form generates a basal effect known as constitutive activity.
The binding affinity of a drug determines its interaction with one...

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Related Experiment Video

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The Development and Application of Biophysical Assays for Evaluating Ternary Complex Formation Induced by Proteolysis Targeting Chimeras (PROTACS)
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The Ran binding protein RanBPM interacts with TrkA receptor.

Yuhe Yuan1, Chengbo Fu, Hong Chen

  • 1National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China.

Neuroscience Letters
|September 9, 2006
PubMed
Summary

RanBPM protein binds to the TrkA receptor, influencing neurotrophin signaling. This interaction affects gene transcription, highlighting RanBPM

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Method for Identifying Small Molecule Inhibitors of the Protein-protein Interaction Between HCN1 and TRIP8b

Published on: November 11, 2016

Area of Science:

  • Molecular Biology
  • Neuroscience
  • Cell Signaling

Background:

  • RanBPM is a novel binding protein interacting with p75NTR and Met receptors.
  • The interaction between RanBPM and neurotrophin receptor TrkA was previously unestablished.

Purpose of the Study:

  • To investigate the interaction between RanBPM and neurotrophin receptor TrkA.
  • To elucidate the functional consequences of this interaction on neurotrophin-mediated signaling.

Main Methods:

  • Yeast two-hybrid system for interaction identification.
  • Co-immunoprecipitation and GST pull-down assays for complex confirmation.
  • Luciferase reporter assay to assess NFAT transcriptional activity.

Main Results:

  • RanBPM binds to the intracellular domain of TrkA via its SPRY motif.
  • Interaction confirmed between RanBPM and TrkA's tyrosine kinase domain.
  • Overexpression of RanBPM inhibits NGF-induced NFAT-dependent gene expression.

Conclusions:

  • RanBPM directly interacts with TrkA, modulating its function.
  • RanBPM plays a role in neurotrophin-mediated gene transcription and expression.
  • This interaction impacts neuronal signal transduction pathways.