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PP2A Affects Angiogenesis via Its Interaction with a Novel Phosphorylation Site of TSP1.
Thalwieser, Zsófia; Fonódi, Márton; Király, Nikolett; Csortos, Csilla; Boratkó, Anita.
Afiliación
  • Thalwieser Z; Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Egyetem tér 1, H-4032 Debrecen, Hungary.
  • Fonódi M; Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Egyetem tér 1, H-4032 Debrecen, Hungary.
  • Király N; Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Egyetem tér 1, H-4032 Debrecen, Hungary.
  • Csortos C; Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Egyetem tér 1, H-4032 Debrecen, Hungary.
  • Boratkó A; Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Egyetem tér 1, H-4032 Debrecen, Hungary.
Int J Mol Sci ; 25(3)2024 Feb 03.
Article en En | MEDLINE | ID: mdl-38339122
ABSTRACT
Alterations in angiogenic properties play a pivotal role in the manifestation and onset of various pathologies, including vascular diseases and cancer. Thrombospondin-1 (TSP1) protein is one of the master regulators of angiogenesis. This study unveils a novel aspect of TSP1 regulation through reversible phosphorylation. The silencing of the B55α regulatory subunit of protein phosphatase 2A (PP2A) in endothelial cells led to a significant decrease in TSP1 expression. Direct interaction between TSP1 and PP2A-B55α was confirmed via various methods. Truncated TSP1 constructs were employed to identify the phosphorylation site and the responsible kinase, ultimately pinpointing PKC as the enzyme phosphorylating TSP1 on Ser93. The biological effects of B55α-TSP1 interaction were also analyzed. B55α silencing not only counteracted the increase in TSP1 expression during wound closure but also prolonged wound closure time. Although B55α silenced cells initiated tube-like structures earlier than control cells, their spheroid formation was disrupted, leading to disintegration. Cells transfected with phosphomimic TSP1 S93D exhibited smaller spheroids and reduced effectiveness in tube formation, revealing insights into the effects of TSP1 phosphorylation on angiogenic properties. In this paper, we introduce a new regulatory mechanism of angiogenesis by reversible phosphorylation on TSP1 S93 by PKC and PP2A B55α.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Endoteliales / Proteína Fosfatasa 2 Límite: Humans Idioma: En Revista: Int J Mol Sci Año: 2024 Tipo del documento: Article País de afiliación: Hungria Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Endoteliales / Proteína Fosfatasa 2 Límite: Humans Idioma: En Revista: Int J Mol Sci Año: 2024 Tipo del documento: Article País de afiliación: Hungria Pais de publicación: Suiza