Opposing TGF-β Actions Explained

Science's STKE  09 Apr 2002:
Vol. 2002, Issue 127, pp. tw129
DOI: 10.1126/stke.2002.127.tw129

Transforming growth factor β (TGF-β) is usually considered an inhibitor of angiogenesis, but it also is reported to stimulate proliferation and migration of endothelial cells. Endothelial cells express two type I TGF-β receptors, ALK1 (activin receptor-like kinase 1) and ALK5, and Goumans et al. propose that it is signaling through these different receptors that accounts for the distinct biological responses. Expression of constitutively active ALK1 or ALK5 in mouse embryonic endothelial cells stimulated or inhibited cell migration, respectively. The differential response of endothelial cells to TGF-β is dose-dependent, and antisense to ALK1-inhibited stimulation of cell migration in response to low doses of TGF-β, whereas antisense to ALK5 reduced the inhibitory effect of high doses of TGF-β. Angiogenesis is a complicated process in which endothelial cells first proliferate and migrate in an "activation" phase and then promote formation of mature blood vessels in a "resolution" phase. The authors propose that changes in the relative expression and activity of ALK1 and ALK5 may help regulate this transition.

M.-J. Goumans, G. Valdimarsdottir, S. Itoh, A. Rosendahl, P. Sideras, P. ten Dijke, Balancing the activation state of the endothelium via two distinct TGF-β type I receptors. EMBO J. 21, 1743-1753 (2002). [Abstract] [Full Text]