Related Experiment Video

Updated: Aug 13, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

A WD-domain protein that is associated with and phosphorylated by the type II TGF-beta receptor

R H Chen1, P J Miettinen, E M Maruoka

  • 1Department of Growth and Development, University of California at San Francisco 94143-0640, USA.

Nature
|October 12, 1995
PubMed

Insights

Researchers discovered TRIP-1, a protein that binds to the type II transforming growth factor-beta (TGF-beta) receptor. This interaction, crucial for TGF-beta signaling, is conserved across eukaryotes, suggesting a fundamental biological role.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Biochemistry

Background:

  • Transforming growth factor-beta (TGF-beta) is a key regulator of cell functions.
  • TGF-beta signaling involves type I and type II serine/threonine kinase receptors forming a complex.
  • The intracellular components interacting with TGF-beta receptors were previously unknown.

Purpose of the Study:

  • To identify cytoplasmic proteins that associate with TGF-beta receptors.
  • To investigate the role of novel proteins in TGF-beta signal transduction.
  • To explore the evolutionary conservation of TGF-beta signaling components.

Main Methods:

  • Protein identification through association with TGF-beta type II receptor.
  • Kinase assays to determine receptor-dependent interactions.
  • Coexpression studies during development.
  • Comparative analysis of TRIP-1 homologues in different species.

Main Results:

  • A WD-domain-containing protein, TRIP-1, was identified.
  • TRIP-1 specifically associates with the TGF-beta type II receptor in a kinase-dependent manner.
  • TRIP-1 interacts with the heteromeric TGF-beta receptor complex but not with activin or type I receptors.
  • TRIP-1 is phosphorylated by the receptor kinase, indicating its role as a potential signaling target.
  • TRIP-1 and type II receptor show coexpression during development.
  • Homologues of TRIP-1 exist in yeast and plants, suggesting conserved function.

Conclusions:

  • TRIP-1 is a novel component of the TGF-beta signaling pathway.
  • TRIP-1's interaction with the TGF-beta receptor complex and its phosphorylation suggest a role in signal transduction.
  • The conserved nature of TRIP-1 points to a fundamental role in eukaryotic biology.

More Related Videos

Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay11:38

Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay

Published on: September 14, 2021

Analysis of Transforming Growth Factor ß Family Cleavage Products Secreted Into the Blastocoele of Xenopus laevis Embryos06:57

Analysis of Transforming Growth Factor ß Family Cleavage Products Secreted Into the Blastocoele of Xenopus laevis Embryos

Published on: July 21, 2021

Related Concept Videos

Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...
Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
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...
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...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...