Jules Dore

Regulation of Cell Growth

The transforming growth factor-beta (TGF-B) family of polypeptide growth factors controls a variety of biological events ranging from gastrulation to wound healing. The focus of my lab is on the three mammalian TGF-Bs (TGF-B1, B2 and B3) and how they modulate a cells replication. The response of a cell to TGF-B depends on the type of cell being affected. Typically, an epithelial or immune cell is growth inhibited while mesenchymal cells are growth stimulated. Although the cell types contain the same receptors and appear to activate the same signal transduction molecules their phenotypic responses are opposite. Current research is focused on investigating the molecular mechanisms that differ between the two cell types with regard to TGF-B receptors and signaling.

1. Molecular mechanism(s) controlling receptor distribution in the plasma membrane of polarized epithelium. A current project involves looking at TGF-B receptors being expressed on the surface of an epithelial layer of cells. I am interested in describing the intrinsic factors (motifs within the amino acid sequence) and extrinsic factors (other proteins) involved in directing the receptors to the cell surface.
   
2. Defining the interactions between proteins associated with TGF-B signaling and internalization of the receptors. Recent studies have shown that TGF-B receptors associate with several other proteins in order to activate the smad signal transduction pathway. Current studies are looking at the make-up of this receptor-protein complex and how it relates to the need for the receptor to be taken up by the cell prior to complex activation.

Recent Publications:

1. Doré JJE, Yao, D, Edens, M, Garamszegi, N, Sholl, EL and Leof EB. 2001. Mechanisms of transforming growth factor-B receptor endocytosis and intracellular sorting differ between fibroblasts and epithelial cells. Molec. Biol. Cell, 12:675-84.
   
2. Garamszegi, N, Doré JJE, Penheiter, SG, Edens, M, Yao, D and Leof EB. 2001. Transforming growth factor B receptor signaling and endocytosis are linked through a COOH terminal activation motif in the type I receptor. Molec. Biol. Cell, 12: 2881-93.
   
3. Doré JJE, Edens, M, Garamszegi, N and Leof EB. 1999. Heteromeric and homomeric transforming growth factor-B receptors show distinct signaling and endocytic responses in epithelial cells. J. Biol. Chem. 273: 31770-77.