A Drosophila MAPKKK, D-MEKK1, mediates stress responses through activation of p38 MAPK

被引:73
作者
Inoue, H
Tateno, M
Fujimura-Kamada, K
Takaesu, G
Adachi-Yamada, T
Ninomiya-Tsuji, J
Irie, K
Nishida, Y
Matsumoto, K [1 ]
机构
[1] Nagoya Univ, Grad Sch Sci, Dept Mol Biol, Nagoya, Aichi 4648602, Japan
[2] Japan Sci & Technol Corp, CREST, Chikusa Ku, Nagoya, Aichi 4648602, Japan
关键词
Drosophila; MAPKKK; p38; MAPK; stress responses;
D O I
10.1093/emboj/20.19.5421
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In cultured mammalian cells, the p38 mitogen-activated protein kinase (MAPK) pathway is activated in response to a variety of environmental stresses. However, there is little evidence from in vivo studies to demonstrate a role for this pathway in the stress response. We identified a Drosophila MAPK kinase kinase (MAPKKK), D-MEKK1, which can activate p38 MAPK. D-MEKK1 is structurally similar to the mammalian MEKK4/MTK1 MAPKKK. D-MEKK1 kinase activity was activated in animals under conditions of high osmolarity. Drosophila mutants lacking D-MEKK1 were hypersensitive to environmental stresses, including elevated temperature and increased osmolarity. In these D-MEKK1 mutants, activation of Drosophila p38 MAPK in response to stress was poor compared with activation in wild-type animals. These results suggest that D-MEKK1 regulation of the p38 MAPK pathway is critical for the response to environmental stresses in Drosophila.
引用
收藏
页码:5421 / 5430
页数:10
相关论文
共 46 条
[1]  
Adachi-Yamada T, 1999, MOL CELL BIOL, V19, P2322
[2]   Distortion of proximodistal information causes JNK-dependent apoptosis in Drosophila wing [J].
Adachi-Yamada, T ;
Fujimura-Kamada, K ;
Nishida, Y ;
Matsumoto, K .
NATURE, 1999, 400 (6740) :166-169
[3]  
Ashburner M., 1989, DROSOPHILA LAB MANUA
[4]   Molecular cloning of mitogen-activated protein ERK kinase kinases (MEKK) 2 and 3 - Regulation of sequential phosphorylation pathways involving mitogen-activated protein kinase and c-Jun kinase [J].
Blank, JL ;
Gerwins, P ;
Elliott, EM ;
Sather, S ;
Johnson, GL .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (10) :5361-5368
[5]   Dishevelled activates JNK and discriminates between JNK pathways in planar polarity and wingless signaling [J].
Boutros, M ;
Paricio, N ;
Strutt, DI ;
Mlodzik, M .
CELL, 1998, 94 (01) :109-118
[6]  
BRAND AH, 1993, DEVELOPMENT, V118, P401
[7]   FUNCTIONAL CDNA LIBRARIES FROM DROSOPHILA EMBRYOS [J].
BROWN, NH ;
KAFATOS, FC .
JOURNAL OF MOLECULAR BIOLOGY, 1988, 203 (02) :425-437
[8]   A CONSERVED BINDING MOTIF DEFINES NUMEROUS CANDIDATE TARGET PROTEINS FOR BOTH CDC42 AND RAC GTPASES [J].
BURBELO, PD ;
DRECHSEL, D ;
HALL, A .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (49) :29071-29074
[9]   G alpha(12) stimulates c-Jun NH2-terminal kinase through the small G proteins Ras and Rac [J].
Collins, LR ;
Minden, A ;
Karin, M ;
Brown, JH .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (29) :17349-17353
[10]   ACTIVATION OF MAP KINASE KINASE IS NECESSARY AND SUFFICIENT FOR PC12 DIFFERENTIATION AND FOR TRANSFORMATION OF NIH 3T3 CELLS [J].
COWLEY, S ;
PATERSON, H ;
KEMP, P ;
MARSHALL, CJ .
CELL, 1994, 77 (06) :841-852