The ins and outs of VEGF signaling.

摘要

In this issue of Blood, Ito and colleagues define a novel extracellular mode of action for the VEGF-A signaling cascade.Vascular endothelial growth factor A (VEGF-A) is bound by an inhibitory factor and, on activation of matrix metallo-proteinase (MMP), the inhibitory factor is cleaved and VEGF-A is available to signal. VEGF is a critical factor in many diverse developmental and disease processes, and the new mode of action discovered by Ito et al provides new understanding of this key pathway.VEGF is normally thought to signal by diffusion from its source to nearby cells expressing critical receptors. However, it has recently been shown that an endogenous form of VEGF-R2 exists as a secreted molecule and includes the VEGF binding extracellular domain. Here, Ito et al ask whether the binding of this factor is permanent or whether it can be released, freeing VEGF for signaling. Indeed, they show that MMP-7 is a secreted protease capable of clipping sVEGF-R2 and releasing an active VEGF protein.