Caldesmon is a cytoskeletal target for PKC in endothelium

Natalia V. Bogatcheva, Anna Birukova, Talaibek Borbiev, Irina Kolosova, Feng Liu, Joe G.N. Garcia, Alexander Dmitriyevich Verin

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

We have previously shown that treatment of bovine endothelial cell (EC) monolayers with phorbol myristate acetate (PMA) leads to the thinning of cortical actin ring and rearrangement of the cytoskeleton into a grid-like structure, concomitant with the loss of endothelial barrier function. In the current work, we focused on caldesmon, a cytoskeletal protein, regulating actomyosin interaction. We hypothesized that protein kinase C (PKC) activation by PMA leads to the changes in caldesmon properties such as phosphorylation and cellular localization. We demonstrate here that PMA induces both myosin and caldesmon redistribution from cortical ring into the grid-like network. However, the initial step of PMA-induced actin and myosin redistribution is not followed by caldesmon redistribution. Co-immunoprecipitation experiments revealed that short-term PMA (5 min) treatment leads to the weakening of caldesmon ability to bind actin and, to the lesser extent, myosin. Prolonged incubation (15-60 min) with PMA, however, strengthens caldesmon complexes with actin and myosin, which correlates with the grid-like actin network formation. PMA stimulation leads to an immediate increase in caldesmon Ser/Thr phosphorylation. This process occurs at sites distinct from the sites specific for ERK1/2 phosphorylation and correlates with caldesmon dissociation from the actomyosin complex. Inhibition of ERK-kinase MEK fails to abolish grid-like structure formation, although reducing PMA-induced weakening of the cortical actin ring, whereas inhibition of PKC reverses PMA-induced cytoskeletal rearrangement. Our results suggest that PKC-dependent phosphorylation of caldesmon is involved in PMA-mediated complex cytoskeletal changes leading to the EC barrier compromise.

Original languageEnglish (US)
Pages (from-to)1593-1605
Number of pages13
JournalJournal of Cellular Biochemistry
Volume99
Issue number6
DOIs
StatePublished - Dec 15 2006
Externally publishedYes

Fingerprint

Calmodulin-Binding Proteins
Cytoskeletal Proteins
Tetradecanoylphorbol Acetate
Protein Kinase C
Endothelium
Actins
Phosphorylation
Myosins
Actomyosin
Endothelial cells
Endothelial Cells
MAP Kinase Kinase Kinases
Cytoskeleton
Immunoprecipitation
Monolayers
Chemical activation

Keywords

  • Caldesmon phosphorylation
  • Cytoskeleton
  • Endothelium
  • PKC

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Bogatcheva, N. V., Birukova, A., Borbiev, T., Kolosova, I., Liu, F., Garcia, J. G. N., & Verin, A. D. (2006). Caldesmon is a cytoskeletal target for PKC in endothelium. Journal of Cellular Biochemistry, 99(6), 1593-1605. https://doi.org/10.1002/jcb.20823

Caldesmon is a cytoskeletal target for PKC in endothelium. / Bogatcheva, Natalia V.; Birukova, Anna; Borbiev, Talaibek; Kolosova, Irina; Liu, Feng; Garcia, Joe G.N.; Verin, Alexander Dmitriyevich.

In: Journal of Cellular Biochemistry, Vol. 99, No. 6, 15.12.2006, p. 1593-1605.

Research output: Contribution to journalArticle

Bogatcheva, NV, Birukova, A, Borbiev, T, Kolosova, I, Liu, F, Garcia, JGN & Verin, AD 2006, 'Caldesmon is a cytoskeletal target for PKC in endothelium', Journal of Cellular Biochemistry, vol. 99, no. 6, pp. 1593-1605. https://doi.org/10.1002/jcb.20823
Bogatcheva NV, Birukova A, Borbiev T, Kolosova I, Liu F, Garcia JGN et al. Caldesmon is a cytoskeletal target for PKC in endothelium. Journal of Cellular Biochemistry. 2006 Dec 15;99(6):1593-1605. https://doi.org/10.1002/jcb.20823
Bogatcheva, Natalia V. ; Birukova, Anna ; Borbiev, Talaibek ; Kolosova, Irina ; Liu, Feng ; Garcia, Joe G.N. ; Verin, Alexander Dmitriyevich. / Caldesmon is a cytoskeletal target for PKC in endothelium. In: Journal of Cellular Biochemistry. 2006 ; Vol. 99, No. 6. pp. 1593-1605.
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AU - Verin, Alexander Dmitriyevich

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