Project: Research project

Project Details


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
Effective start/end date5/1/974/30/19


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