2026-07-22T20:10:59Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/100082024-11-29T20:03:15Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Serra, Helena author Chivite, Iñigo author Angulo-Urarte, Ana author Soler, Adriana author Sutherland, James D author Arruabarrena-Aristorena, Amaia author Ragab, Anan author Lim, Radiance author Malumbres Martinez, Marcos author Fruttiger, Marcus author Potente, Michael author Serrano Marugan, Manuel author Fabra, Àngels author Viñals, Francesc author Casanovas, Oriol author Pandolfi, Pier Paolo author Bigas, Anna author Carracedo, Arkaitz author Gerhardt, Holger author Graupera, Mariona author 2015-07-31 Coordinated activity of VEGF and Notch signals guides the endothelial cell (EC) specification into tip and stalk cells during angiogenesis. Notch activation in stalk cells leads to proliferation arrest via an unknown mechanism. By using gain- and loss-of-function gene-targeting approaches, here we show that PTEN is crucial for blocking stalk cell proliferation downstream of Notch, and this is critical for mouse vessel development. Endothelial deletion of PTEN results in vascular hyperplasia due to a failure to mediate Notch-induced proliferation arrest. Conversely, overexpression of PTEN reduces vascular density and abrogates the increase in EC proliferation induced by Notch blockade. PTEN is a lipid/protein phosphatase that also has nuclear phosphatase-independent functions. We show that both the catalytic and non-catalytic APC/C-Fzr1/Cdh1-mediated activities of PTEN are required for stalk cells' proliferative arrest. These findings define a Notch-PTEN signalling axis as an orchestrator of vessel density and implicate the PTEN-APC/C-Fzr1/Cdh1 hub in angiogenesis. Nat Commun. 2015;6:7935 10.1038/ncomms8935 2041-1723 2041-1723 Nature communications 26228240 http://hdl.handle.net/20.500.12105/10008 PTEN mediates Notch-dependent stalk cell arrest in angiogenesis