ROCK-II-induced membrane blebbing and chromatin condensation require actin cytoskeleton

被引:41
作者
Song, YH [1 ]
Hoang, BQ [1 ]
Chang, DD [1 ]
机构
[1] Univ Calif Los Angeles, Sch Med, Div Heme Onc, Dept Med Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA
关键词
Rho GTPase; apoptosis; tetracycline-inducible expression; actin filaments; cofilin; ML-7; caspase-3; z-VAD-fmk; MCF-7;
D O I
10.1006/excr.2002.5565
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Ectopic expression of ROCK II (Rho kinase II or ROKalpha), an effector of Rho GTPase, induces membrane blebbing and chromatin condensation. ROCK 11 can induce membrane blebbing in the presence of the caspase inhibitor z-VAD-fmk or in caspase-3-deficient MCF-7 cells, indicating that the activation of caspases is not required. ROCK-II-induced membrane blebbing, however, is reversed by the myosin light chain kinase inhibitor ML-7 or cytochalasin D. In addition, the expression of a constitutively activated form of cofilin (S3A-cofilin) suppresses both membrane blebbing and chromatin condensation in ROCK II expressing cells. These findings suggest that the activation of actin-myosin contractility is responsible for membrane blebbing and chromatin condensation and implicate ROCK II as a potential mediator of the morphological changes associated with apoptosis. (C) 2002 Elsevier Science (USA).
引用
收藏
页码:45 / 52
页数:8
相关论文
共 39 条
[11]   Rho GTPases and the actin cytoskeleton [J].
Hall, A .
SCIENCE, 1998, 279 (5350) :509-514
[12]   Interactions of protein phosphatase type 1, with a focus on myosin phosphatase [J].
Hartshorne, DJ ;
Hirano, K .
MOLECULAR AND CELLULAR BIOCHEMISTRY, 1999, 190 (1-2) :79-84
[13]   The small GTP-binding protein Rho binds to and activates a 160 kDa Ser/Thr protein kinase homologous to myotonic dystrophy kinase [J].
Ishizaki, T ;
Maekawa, M ;
Fujisawa, K ;
Okawa, K ;
Iwamatsu, A ;
Fujita, A ;
Watanabe, N ;
Saito, Y ;
Kakizuka, A ;
Morii, N ;
Narumiya, S .
EMBO JOURNAL, 1996, 15 (08) :1885-1893
[14]   THE FUNCTION OF MYOSIN AND MYOSIN LIGHT CHAIN KINASE PHOSPHORYLATION IN SMOOTH-MUSCLE [J].
KAMM, KE ;
STULL, JT .
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, 1985, 25 :593-620
[15]   Cleavage of actin by interleukin 1 beta-converting enzyme to reverse DNase I inhibition [J].
Kayalar, C ;
Ord, T ;
Testa, MP ;
Zhong, LT ;
Bredesen, DE .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (05) :2234-2238
[16]   Regulation of myosin phosphatase by Rho and Rho-Associated kinase (Rho-kinase) [J].
Kimura, K ;
Ito, M ;
Amano, M ;
Chihara, K ;
Fukata, Y ;
Nakafuku, M ;
Yamamori, B ;
Feng, JH ;
Nakano, T ;
Okawa, K ;
Iwamatsu, A ;
Kaibuchi, K .
SCIENCE, 1996, 273 (5272) :245-248
[17]   Caspase-3-generated fragment of gelsolin: Effector of morphological change in apoptosis [J].
Kothakota, S ;
Azuma, T ;
Reinhard, C ;
Klippel, A ;
Tang, J ;
Chu, KT ;
McGarry, TJ ;
Kirschner, MW ;
Koths, K ;
Kwiatkowski, DJ ;
Williams, LT .
SCIENCE, 1997, 278 (5336) :294-298
[18]  
Kurokawa H, 1999, ONCOL REP, V6, P33
[19]   CONTRACTILE PROTEINS - MAJOR COMPONENTS OF NUCLEAR AND CHROMOSOME NONHISTONE PROTEINS [J].
LESTOURGEON, WM ;
FORER, A ;
YANG, YZ ;
BERTRAM, JS ;
RUSCH, HP .
BIOCHIMICA ET BIOPHYSICA ACTA, 1975, 379 (02) :529-552
[20]  
Leung T, 1996, MOL CELL BIOL, V16, P5313