Regulation of angiogenesis by a small GTPase Rap1

Small GTPase Rap1 has been extensively studied in vitro and shown to regulate multiple basic cellular processes. Until recently, the best studied aspect of Rap1 function in endothelial cells involved its role in regulation of cell–cell junction formation and remodeling. These in vitro studies have increased understanding of the molecular players regulating Rap1 activity, including mechanisms through which Rap1 regulates endothelial permeability. Several recent reports provide emerging evidence that Rap1 function in endothelial cells is not limited to promoting barrier but that it also regulates basic endothelial responses to angiogenic stimulation and that Rap1 may act as a positive regulator of angiogenesis in vivo. This article provides an overview of these findings in the context of the existing knowledge of the function of the two Rap1 isoforms, followed by speculation regarding potential mechanisms through which Rap1 proteins may be regulating angiogenesis.