Protein Phosphatase 2A Mediates YAP Activation in Endothelial Cells Upon VEGF Stimulation and Matrix Stiffness.
Protein Phosphatase 2A Mediates YAP Activation in Endothelial Cells Upon VEGF Stimulation and Matrix Stiffness.
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蛋白磷酸酶 2A 在 VEGF 刺激和基质硬度下介导内皮细胞中 YAP 激活
DOI：
10.3389/fcell.2021.675562
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发表时间：
2021
影响因子：
5.5
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Jiang X;Hu J;Wu Z;Cafarello ST;Di Matteo M;Shen Y;Dong X;Adler H;Mazzone M;Ruiz de Almodovar C;Wang X
Angiogenesis is an essential process during development. Abnormal angiogenesis also contributes to many disease conditions such as tumor and retinal diseases. Previous studies have established the Hippo signaling pathway effector Yes-associated protein (YAP) as a crucial regulator of angiogenesis. In ECs, activated YAP promotes endothelial cell proliferation, migration and sprouting. YAP activity is regulated by vascular endothelial growth factor (VEGF) and mechanical cues such as extracellular matrix (ECM) stiffness. However, it is unclear how VEGF or ECM stiffness signal to YAP, especially how dephosphorylation of YAP occurs in response to VEGF stimulus or ECM stiffening. Here, we show that protein phosphatase 2A (PP2A) is required for this process. Blocking PP2A activity abolishes VEGF or ECM stiffening mediated YAP activation. Systemic administration of a PP2A inhibitor suppresses YAP activity in blood vessels in developmental and pathological angiogenesis mouse models. Consistently, PP2A inhibitor also inhibits sprouting angiogenesis. Mechanistically, PP2A directly interacts with YAP, and this interaction requires proper cytoskeleton dynamics. These findings identify PP2A as a crucial mediator of YAP activation in ECs and hence as an important regulator of angiogenesis.
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影响因子：
64.8
作者：
Chang L;Azzolin L;Di Biagio D;Zanconato F;Battilana G;Lucon Xiccato R;Aragona M;Giulitti S;Panciera T;Gandin A;Sigismondo G;Krijgsveld J;Fassan M;Brusatin G;Cordenonsi M;Piccolo S
通讯作者：
Piccolo S
影响因子：
4.8
作者：
Evans, DRH;Myles, T;Hemmings, BA
通讯作者：
Hemmings, BA
影响因子：
7.7
作者：
Carvalho, Joana R.;Fortunato, Isabela C.;Franco, Claudio A.
通讯作者：
Franco, Claudio A.
影响因子：
11.4
作者：
Martin, Maud;Geudens, Ilse;Dequiedt, Franck
通讯作者：
Dequiedt, Franck
靶向NCK介导的内皮细胞前射线极性会抑制新血管形成。
影响因子：
37.8
作者：
Dubrac A;Genet G;Ola R;Zhang F;Pibouin-Fragner L;Han J;Zhang J;Thomas JL;Chedotal A;Schwartz MA;Eichmann A
通讯作者：
Eichmann A