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

被引：44

作者：

Chang, Eugene ^{[1
,2
,3
]}

Heo, Kyung-Sun ^{[1
,2
]}

Woo, Chang-Hoon ^{[1
,2
]}

Lee, Hakjoo ^{[1
,2
]}

Le, Nhat-Tu ^{[1
,2
]}

Thomas, Tamlyn N. ^{[1
,2
]}

Fujiwara, Keigi ^{[1
,2
]}

Abe, Jun-ichi ^{[1
,2
,3
]}

机构：

[1] Univ Rochester, Sch Med & Dent, Aab Cardiovasc Res Inst, Rochester, NY 14642 USA

[2] Univ Rochester, Sch Med & Dent, Dept Med, Rochester, NY 14642 USA

[3] Univ Rochester, Sch Med & Dent, Dept Pathol & Lab Med, Rochester, NY 14642 USA

来源：

BLOOD | 2011年 / 117卷 / 08期

基金：

美国国家卫生研究院;

关键词：

P38 MAP KINASE; TUMOR-NECROSIS-FACTOR; FLUID SHEAR-STRESS; HEAT-SHOCK PROTEIN-27; ACTIVATION; REORGANIZATION; ANGIOGENESIS; EXPRESSION; DYNAMICS; PATHWAY;

D O I：

10.1182/blood-2010-08-302281

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

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)

引用

页码：2527 / 2537

页数：11

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