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Sci. Signal., 26 October 2010
Vol. 3, Issue 145, p. ra76
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 (PI3K), 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 PI3K. Thus, ARAP3 is downstream of PI3K in the regulation of sprouting angiogenesis during development and could be targeted in antiangiogenic therapies.
Citation: L. Gambardella, M. Hemberger, B. Hughes, E. Zudaire, S. Andrews, S. Vermeren, PI3K Signaling Through the Dual GTPase–Activating Protein ARAP3 Is Essential for Developmental Angiogenesis. Sci. Signal.3, ra76 (2010).
The GTPase-activating protein ARAP3 regulates chemotaxis and adhesion-dependent processes in neutrophils.
L. Gambardella, K. E. Anderson, C. Nussbaum, A. Segonds-Pichon, T. Margarido, L. Norton, T. Ludwig, M. Sperandio, P. T. Hawkins, L. Stephens, et al. (2011)
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