Edg-1 was cloned as an novel immediate-early response gene induced following phorbol ester stimulation of human umbilical vein endothelial cell differentiation. The deduced amino acid sequence of the edg-1 protein suggest that it is a seven-pass transmembrane receptor. The edg-1 ligand is currently unknown and so edg-1 is classified as an orphan receptor. Edg-1 couples to the Gi family of polypeptides and initiates sustained activation the mitogen activated protein kinase pathway. Sustained activation of the MAP kinase pathway is required for cellular differentiation in PC-12 neuronal cells and morphologic differentiation in Dictyostelium. Edg-1 overexpression results in morphologic differentiation of HEK293 cells by suppressing cell-matrix adhesion, upregulating E- and P-cadherins and inducing cell-cell adhesion. These findings support the central hypothesis of this proposal which is that in vascular endothelial cells edg-1 signaling regulates the morphogenetic differentiation phase of the angiogenic response. The objective of this proposal is to define the signaling pathways involved in this morphogenetic differentiation, as well as definition of the phenotype of the edg-1-induced differentiated state.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK045659-05
Application #
2410078
Study Section
Pathology A Study Section (PTHA)
Program Officer
Linder, Barbara
Project Start
1992-09-30
Project End
2002-08-31
Budget Start
1997-09-30
Budget End
1998-08-31
Support Year
5
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Connecticut
Department
Anatomy/Cell Biology
Type
Schools of Dentistry
DUNS #
City
Farmington
State
CT
Country
United States
Zip Code
06030
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