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

Title
MK2 SUMOylation regulates actin filament remodeling and subsequent migration in endothelial cells by inhibiting MK2 kinase and HSP27 phosphorylation
Author(s)
우창훈Chang E[Chang E]Heo KS[Heo KS]Lee H[Lee H]Le NT[Le NT]Thomas TN[Thomas TN]Fujiwara K[Fujiwara K]Abe J[Abe J]
Keywords
P38 MAP KINASE; TUMOR-NECROSIS-FACTOR; FLUID SHEAR-STRESS; HEAT-SHOCK PROTEIN-27; ACTIVATION; REORGANIZATION; ANGIOGENESIS; EXPRESSION; DYNAMICS; PATHWAY
Issue Date
201102
Publisher
AMER SOC HEMATOLOGY
Citation
BLOOD, v.117, no.8, pp.2527 - 2537
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-alpha (TNF-alpha) 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-alpha-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. (Blood. 2011;117(8):2527-2537)
URI
http://hdl.handle.net/YU.REPOSITORY/25651http://dx.doi.org/10.1182/blood-2010-08-302281
ISSN
0006-4971
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의과대학 > 약리학교실 > Articles
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