Role of protein phosphatase 2A in the regulation of endothelial cell cytoskeleton structure

Krisztina Tar, C. Csortos, Istvan Czikora, Gabor Olah, Shwu Fan Ma, Raj Wadgaonkar, P. Gergely, Joe G N Garcia, Alexander D. Verin

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Our recently published data suggested the involvement of protein phosphatase 2A (PP2A) in endothelial cell (EC) barrier regulation (Tar et al. [2004] J Cell Biochem 92:534-546). In order to further elucidate the role of PP2A in the regulation of EC cytoskeleton and permeability, PP2A catalytic (PP2Ac) and A regulatory (PP2Aa)subunits were cloned and human pulmonary arterial EC (HPAEC) were transfected with PP2A mammalian expression constructs or infected with PP2A recombinant adenoviruses. Immunostaining of PP2Ac or of PP2Aa + c overexpressing HPAEC indicated actin cytoskeleton rearrangement. PP2A overexpression hindered or at least dramatically reduced thrombin- or nocodazole-induced F-actin stress fiber formation and microtubule (MT) dissolution. Accordingly, it also attenuated thrombin- or nocodazole-induced decrease in transendothelial electrical resistance indicative of barrier protection. Inhibition of PP2A by okadaic acid abolished its effect on agonist-induced changes in EC cytoskeleton; this indicates a critical role of PP2A activity in EC cytoskeletal maintenance. The overexpression of PP2A significantly attenuated thrombin- or nocodazole-induced phosphorylation of HSP27 and tau, two cytoskeletal proteins, which potentially could be involved in agonist-induced cytoskeletal rearrangement and in the increase of permeability. PP2A-mediated dephosphorylation of HSP27 and tau correlated with PP2A-induced preservation of EC cytoskeleton and barrier maintenance. Collectively, our observations clearly demonstrate the crucial role of PP2A in EC barrier protection.

Original languageEnglish
Pages (from-to)931-953
Number of pages23
JournalJournal of Cellular Biochemistry
Volume98
Issue number4
DOIs
Publication statusPublished - Jul 1 2006

Fingerprint

Protein Phosphatase 2
Endothelial cells
Cytoskeleton
Endothelial Cells
Nocodazole
Thrombin
Permeability
Actins
Maintenance
Okadaic Acid
Lung
Stress Fibers
Phosphorylation
Acoustic impedance
Cytoskeletal Proteins
Cytoprotection
Electric Impedance
Actin Cytoskeleton
Adenoviridae
Microtubules

Keywords

  • Endothelium
  • HSP27
  • Microfilaments
  • Microtubules
  • Permeability
  • Phosphatase 2A
  • Tau

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

Role of protein phosphatase 2A in the regulation of endothelial cell cytoskeleton structure. / Tar, Krisztina; Csortos, C.; Czikora, Istvan; Olah, Gabor; Ma, Shwu Fan; Wadgaonkar, Raj; Gergely, P.; Garcia, Joe G N; Verin, Alexander D.

In: Journal of Cellular Biochemistry, Vol. 98, No. 4, 01.07.2006, p. 931-953.

Research output: Contribution to journalArticle

Tar, Krisztina ; Csortos, C. ; Czikora, Istvan ; Olah, Gabor ; Ma, Shwu Fan ; Wadgaonkar, Raj ; Gergely, P. ; Garcia, Joe G N ; Verin, Alexander D. / Role of protein phosphatase 2A in the regulation of endothelial cell cytoskeleton structure. In: Journal of Cellular Biochemistry. 2006 ; Vol. 98, No. 4. pp. 931-953.
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