Affiliation:
1. Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Abstract
Cytokines of the transforming growth factor-β (TGF-β) superfamily transduce their signals by activating receptor-regulated Smads (R-Smads). Distinct R-Smads or combinations of R-Smads are activated by TGF-β, activin, or bone morphogenetic proteins (BMPs). R-Smads activated by BMPs induce expression of Id proteins, which act as inhibitors of differentiation and stimulators of cell growth by inhibiting the function of basic helix-loop-helix transcription factors. In endothelial cells, TGF-β binds to two distinct type I receptor serine-threonine kinases, ALK-5 and ALK-1; the latter activates the same R-Smads that are activated by BMP and induces synthesis of Id (inhibitor of differentation or inhibitor of DNA binding) proteins. Growing evidence suggests that Id proteins may play crucial roles in angiogenesis, neurogenesis, and osteogenesis and act as key molecules in regulating biological responses induced by BMPs and TGF-β.
Publisher
American Association for the Advancement of Science (AAAS)