Anthrax lethal factor causes proteolytic inactivation of mitogen-activated protein kinase kinase

被引：32

作者：

Duesbery, NS

Vande Woude, GF

机构：

[1] NCI, Frederick Canc Res & Dev Ctr, Div Basic Sci, Frederick, MD 21702 USA

[2] NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA

来源：

JOURNAL OF APPLIED MICROBIOLOGY | 1999年 / 87卷 / 02期

关键词：

D O I：

10.1046/j.1365-2672.1999.00892.x

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

A search of the National Cancer Institute's Anti-Neoplastic Drug Screen for compounds with; an inhibitory profile similar to that of the mitogen-activated protein kinase kinase (MAPKK) inhibitor PD098059 yielded anthrax lethal toxin. Anthrax lethal factor was found to inhibit progesterone-induced meiotic maturation of frog oocytes by preventing the phosphorylation and activation of mitogen-activated protein kinase (MAPK). Similarly, lethal tor;in prevented the activation of MAPK in serum stimulated, ras-transformed NIH3T3 cells. In vitro analyses using recombinant proteins indicated that lethal factor proteolytically modified the NH2-terminus of both MAPKK1 and 2, rendering them inactive and hence incapable of activating MAPK. The consequences of this inactivation upon meiosis and transformed cells are also discussed.

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页码：289 / 293

页数：5

相关论文

共 32 条

[1] Mos/mitogen-activated protein kinase can induce early meiotic phenotypes in the absence of maturation-promoting factor: A novel system for analyzing spindle formation during meiosis I [J].

Choi, T ;

Rulong, S ;

Resau, J ;

Fukasawa, K ;

Matten, W ;

Kuriyama, R ;

Mansour, S ;

Ahn, N ;

VandeWoude, GF .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (10) :4730-4735

[2] A SYNTHETIC INHIBITOR OF THE MITOGEN-ACTIVATED PROTEIN-KINASE CASCADE [J].

DUDLEY, DT ;

PANG, L ;

DECKER, SJ ;

BRIDGES, AJ ;

SALTIEL, AR .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (17) :7686-7689

[3] Proteolytic inactivation of MAP-kinase-kinase by anthrax lethal factor [J].

Duesbery, NS ;

Webb, CP ;

Leppla, SH ;

Gordon, VM ;

Klimpel, KR ;

Copeland, TD ;

Ahn, NG ;

Oskarsson, MK ;

Fukasawa, K ;

Paull, KD ;

Vande Woude, GF .

SCIENCE, 1998, 280 (5364) :734-737

[4] CELL-CYCLE TYROSINE PHOSPHORYLATION OF P34CDC2 AND A MICROTUBULE-ASSOCIATED PROTEIN-KINASE HOMOLOG IN XENOPUS OOCYTES AND EGGS [J].

FERRELL, JE ;

WU, M ;

GERHART, JC ;

MARTIN, GS .

MOLECULAR AND CELLULAR BIOLOGY, 1991, 11 (04) :1965-1971

[5] Synergy between the Mos/mitogen-activated protein kinase pathway and loss of p53 function in transformation and chromosome instability [J].

Fukasawa, K ;

VandeWoude, GF .

MOLECULAR AND CELLULAR BIOLOGY, 1997, 17 (01) :506-518

[6] XENOPUS M-PHASE MAP KINASE - ISOLATION OF ITS CDNA AND ACTIVATION BY MPF [J].

GOTOH, Y ;

MORIYAMA, K ;

MATSUDA, S ;

OKUMURA, E ;

KISHIMOTO, T ;

KAWASAKI, H ;

SUZUKI, K ;

YAHARA, I ;

SAKAI, H ;

NISHIDA, E .

EMBO JOURNAL, 1991, 10 (09) :2661-2668

[7] INDUCTION OF XENOPUS OOCYTE MEIOTIC MATURATION BY MAP KINASE [J].

HACCARD, O ;

LEWELLYN, A ;

HARTLEY, RS ;

ERIKSON, E ;

MALLER, JL .

DEVELOPMENTAL BIOLOGY, 1995, 168 (02) :677-682

[8] INVIVO ACTIVATION OF A MICROTUBULE-ASSOCIATED PROTEIN-KINASE DURING MEIOTIC MATURATION OF THE XENOPUS OOCYTE [J].

HACCARD, O ;

JESSUS, C ;

CAYLA, X ;

GORIS, J ;

MERLEVEDE, W ;

OZON, R .

EUROPEAN JOURNAL OF BIOCHEMISTRY, 1990, 192 (03) :633-642

[9] Lethal factor active-site mutations affect catalytic activity in vitro [J].

Hammond, SE ;

Hanna, PC .

INFECTION AND IMMUNITY, 1998, 66 (05) :2374-2378

[10]

JESSUS C, 1991, DEVELOPMENT, V111, P813

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