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Control of angiogenesis is critical in diseases such as cancer, heart disease, or wound repair. Growth factors such as transforming growth factor beta (TGFs) and fibroblast growth factor 2 (FGF-2) contribute to angiogenesis. The TGFs family signaling receptor Activin-Like Kinase 1 Receptor (ALK-1) is expressed in coronary venular endothelial cells (CVEC) at near confluent cell densities on gelatin, but not collagen but it is induced by TGFs + FGF-2 during tube formation in collagen. Other genes induced during tube formation were Smad 6 and Fibroblast Growth Factor Receptor 1 (FGFR1). By contrast, ALK-5, a related TGFs type 1 receptor, and TGFsRII were expressed in these cells in both gelatin and collagen. ALK-1 is also expressed in other EC types, smooth muscle cells, cardiac fibroblasts, embryonic fibroblasts (3T3) but not epithelial cells. Three ligands: TGFs, activin, and bone morphogenetic protein 9 (BMP-9), have been shown to bind ALK-1. We show that endogenous activin binds ALK 1 and can be displace...