TGF BETA RECEPTOR DYNAMICS

Project: Research project

Description

DESCRIPTION: The hypothesis to be investigated is that distinct elements within the cytoplasmic and/or transmembrane domain(s) of the type 1 and type 2 TGF-beta heteromeric receptors mediate heteromeric receptor association with clathrin coated pit proteins and receptor downregulation. Since the homomeric type 1 or type 2 receptors can be internalized but are not down-regulated and cannot signal, it is further hypothesized that there is ligand dependent crosstalk between the heteromeric partners. A chimeric TGF-beta receptor model will be used for the proposed studies: murine AKR-2B mesenchymal (fibroblast) cell clones expressing chimeric TGF-beta receptors consisting of the extracellular ligand binding domain of the GM-CSF alpha or beta receptors fused with the transmembrane and cytoplasmic domain of the type 1 or type 2 TGF-beta receptors. This chimeric model system permits investigation of the signaling capacity of TGF-beta receptor type 1/type 1 homomers, type 2/type 2 homomers and type1/type 2 heteromers. The specific aims are: 1. identification and characterization of the receptor elements mediating downregulation of heteromeric type 1/type 2 receptor complexes; 2. determination how TGF-beta receptors are sorted following association with the clathrin lattice; 3. determination whether TGF-beta receptor kinase activity or phosphorylation modulates receptor trafficking.
StatusFinished
Effective start/end date5/1/974/30/19

Funding

  • National Institutes of Health: $381,600.00
  • National Institutes of Health: $340,614.00
  • National Institutes of Health: $293,155.00
  • National Institutes of Health: $344,055.00
  • National Institutes of Health
  • National Institutes of Health: $347,530.00
  • National Institutes of Health: $301,910.00
  • National Institutes of Health: $381,600.00
  • National Institutes of Health: $253,980.00
  • National Institutes of Health: $309,175.00
  • National Institutes of Health: $340,614.00
  • National Institutes of Health: $253,980.00
  • National Institutes of Health: $328,692.00
  • National Institutes of Health: $293,155.00
  • National Institutes of Health: $227,384.00
  • National Institutes of Health: $253,980.00
  • National Institutes of Health: $253,980.00
  • National Institutes of Health
  • National Institutes of Health: $381,600.00
  • National Institutes of Health

Fingerprint

Transforming Growth Factor beta Receptors
Transforming Growth Factor beta
Epithelial Cells
Growth
Sorting Nexins
Clathrin
Endocytosis
Phenotype
Intercellular Signaling Peptides and Proteins
Ligands
Cell Membrane
Fibrosis

ASJC

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)