MK2 SUMOylation regulates actin filament remodeling and subsequent migration in endothelial cells by inhibiting MK2 kinase and HSP27 phosphorylation

Eugene Chang, Kyung-Sun Heo, Chang-Hoon Woo, Hakjoo Lee, Nhat-Tu Le, Tamlyn N Thomas, Keigi Fujiwara, Jun-ichi Abe

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Actin filament remodeling regulates several endothelial cell (EC) processes such as contraction, migration, adhesion, and shape determination. Mitogen-activated protein kinase (MAPK)-activated protein kinase 2 (MK2)-mediated phosphorylation of heat-shock protein 27 kDa (HSP27) promotes actin filament remodeling, but little is known about the regulation of this event in ECs. We found that tumor necrosis factor-α (TNF-α) SUMOylated MK2 at lysine (K)-339 affected EC actin filament organization and migration. Loss of the MK2 SUMOylation site (MK2-K339R) increased MK2 kinase activity and prolonged HSP27 phosphorylation, enhancing its effects on actin filament-dependent events. Both TNF-α-mediated EC elongation and steady laminar shear stress-mediated EC alignment were increased by MK2-K339R. Moreover, kinase-dead dominant-negative MK2 (DN-MK2) inhibited these effects. Cell migration is a dynamic process regulated by actin filament remodeling. Both wild-type MK2 (WT-MK2) and DN-MK2 significantly enhanced TNF-mediated inhibition of EC migration, and MK2-K339R further augmented this effect. Interestingly, the p160-Rho-associated coiled-coil kinase (ROCK) inhibitor Y-27632 reversed this effect by MK2-K339R, which strongly suggests that both excessive and insufficient levels of actin filament remodeling can block EC migration. Our study shows that MK2 SUMOylation is a new mechanism for regulating actin filament dynamics in ECs.

Original languageEnglish (US)
Pages (from-to)2527-37
Number of pages11
JournalBlood
Volume117
Issue number8
DOIs
StatePublished - Feb 24 2011

Keywords

  • Actin Cytoskeleton
  • Binding Sites
  • Cell Movement
  • Cells, Cultured
  • Endothelial Cells
  • Endothelium, Vascular
  • HSP27 Heat-Shock Proteins
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Phosphorylation
  • Protein-Serine-Threonine Kinases
  • Sumoylation
  • Tumor Necrosis Factor-alpha
  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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