Research ArticleDevelopmental Biology

PI3K Signaling Through the Dual GTPase–Activating Protein ARAP3 Is Essential for Developmental Angiogenesis

Sci. Signal.  26 Oct 2010:
Vol. 3, Issue 145, pp. ra76
DOI: 10.1126/scisignal.2001026

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ARAP3 for Angiogenesis

Angiogenesis is the process by which new blood vessels are formed. In addition to being a developmentally critical process, angiogenesis enables the growth and metastasis of solid tumors and occurs during wound healing. Previous work indicated that the activity of phosphoinositide 3-kinase α (PI3Kα), which generates the lipid second messenger PtdIns(3,4,5)P3, is required for a form of angiogenesis called sprouting angiogenesis. ARAP3 is a guanosine triphosphatase–activating protein (GAP) that is stimulated by PtdIns(3,4,5)P3. Gambardella et al. found that mice lacking ARAP3 or expressing a form of ARAP3 that cannot be activated by PtdIns(3,4,5)P3 had defects in sprouting angiogenesis reminiscent of those seen in mice expressing a catalytically inactive form of PI3Kα. Thus, ARAP3 is downstream of PI3K in the regulation of sprouting angiogenesis during development and could be targeted in antiangiogenic therapies.