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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.
Pubmed ID: 34055807 RIS Download
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A comparative platform for green plant genomics. Families of orthologous and paralogous genes that represent the modern descendents of ancestral gene sets are constructed at key phylogenetic nodes. These families allow easy access to clade specific orthology / paralogy relationships as well as clade specific genes and gene expansions. As of release v9.1, Phytozome provides access to forty-one sequenced and annotated green plant genomes which have been clustered into gene families at 20 evolutionarily significant nodes. Where possible, each gene has been annotated with PFAM, KOG, KEGG, and PANTHER assignments, and publicly available annotations from RefSeq, UniProt, TAIR, JGI are hyper-linked and searchable.
View all literature mentionsA comparative platform for green plant genomics. Families of orthologous and paralogous genes that represent the modern descendents of ancestral gene sets are constructed at key phylogenetic nodes. These families allow easy access to clade specific orthology / paralogy relationships as well as clade specific genes and gene expansions. As of release v9.1, Phytozome provides access to forty-one sequenced and annotated green plant genomes which have been clustered into gene families at 20 evolutionarily significant nodes. Where possible, each gene has been annotated with PFAM, KOG, KEGG, and PANTHER assignments, and publicly available annotations from RefSeq, UniProt, TAIR, JGI are hyper-linked and searchable.
View all literature mentionsA comparative platform for green plant genomics. Families of orthologous and paralogous genes that represent the modern descendents of ancestral gene sets are constructed at key phylogenetic nodes. These families allow easy access to clade specific orthology / paralogy relationships as well as clade specific genes and gene expansions. As of release v9.1, Phytozome provides access to forty-one sequenced and annotated green plant genomes which have been clustered into gene families at 20 evolutionarily significant nodes. Where possible, each gene has been annotated with PFAM, KOG, KEGG, and PANTHER assignments, and publicly available annotations from RefSeq, UniProt, TAIR, JGI are hyper-linked and searchable.
View all literature mentionsCell line HUVEC-C is a Finite cell line with a species of origin Homo sapiens
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsThe SciCrunch Infrastructure was developed as a cooperative data platform to be used by diverse communities in making data more FAIR.
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