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001-es BibID:BIBFORM118568
035-os BibID:(cikkazonosító)1844 (WoS)001160100000001 (Scopus)85184739282
Első szerző:Thalwieser Zsófia (biológus)
Cím:PP2A Affects Angiogenesis via Its Interaction with a Novel Phosphorylation Site of TSP1 / Thalwieser Zsófia, Fonódi Márton, Király Nikolett, Csortos Csilla, Boratkó Anita
Dátum:2024
ISSN:1422-0067
Megjegyzések: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 B55 alpha regulatory subunit of protein phosphatase 2A (PP2A) in endothelial cells led to a significant decrease in TSP1 expression. Direct interaction between TSP1 and PP2A-B55 alpha 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 B55 alpha-TSP1 interaction were also analyzed. B55 alpha silencing not only counteracted the increase in TSP1 expression during wound closure but also prolonged wound closure time. Although B55 alpha 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 B55 alpha.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
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Megjelenés:International Journal Of Molecular Sciences. - 25 : 3 (2024), p. 1-23. -
További szerzők:Fonódi Márton (1995-) (molekuláris biológus) Király Nikolett (1992-) (molekuláris biológus, biokémikus) Csortos Csilla (1956-) (biokémikus) Boratkó Anita (1985-) (biokémikus, molekuláris biológus)
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