Related Experiment Video

Updated: Jun 1, 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

Structures of TGF-β receptor complexes: implications for function and therapeutic intervention using ligand traps

Andrew P Hinck1, Maureen D O'Connor-McCourt

  • 1Department of Biochemistry, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA. hinck@uthscsa.edu

Current Pharmaceutical Biotechnology
|May 31, 2011
PubMed

Insights

Transforming growth factor-beta (TGF-β) isoforms are crucial signaling molecules involved in cell growth and development. This review details their structures, receptor interactions, and potential for targeted therapies in diseases like fibrosis and cancer.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Structural Biology

Background:

  • Transforming growth factor-beta (TGF-β) isoforms (TGF-β1, -β2, -β3) are key signaling ligands.
  • They regulate extracellular matrix, cell growth, differentiation, immune function, and organ development.
  • Dysregulation of TGF-β signaling is implicated in human diseases like fibrosis and cancer.

Purpose of the Study:

  • To review recent advances in characterizing TGF-β isoform structures bound to their receptors.
  • To compare these structures with each other and with other superfamily members.
  • To explore how structural insights inform distinct isoform functions and therapeutic strategies.

Main Methods:

  • Structural biology techniques (e.g., X-ray crystallography, cryo-EM) to determine TGF-β-receptor complexes.
  • Biophysical studies to analyze binding affinities and interactions.
  • Comparative analysis of structural data across TGF-β isoforms and related proteins.

Main Results:

  • Structural and biophysical data highlight the shared evolutionary origins of TGF-β isoforms.
  • Specific structural differences explain how isoforms diverge to perform distinct biological roles.
  • Understanding isoform-receptor interactions reveals opportunities for targeted therapeutic interventions.

Conclusions:

  • Structural characterization of TGF-β isoforms and their receptors provides critical insights into their diverse functions.
  • These findings pave the way for developing novel therapeutic strategies, including isoform-specific ligand traps.
  • Targeting TGF-β signaling holds promise for treating fibrotic and cancerous diseases.

More Related Videos

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

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

Related Concept Videos

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...
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,...
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:
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...
G Protein-coupled Receptors01:15

G Protein-coupled Receptors

G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
Ligand Binding Sites02:40

Ligand Binding Sites

Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...