Wnt activates the Tak1/Nemo-like kinase pathway

被引:95
作者
Smit, L [1 ]
Baas, A [1 ]
Kuipers, J [1 ]
Korswagen, H [1 ]
van de Wetering, M [1 ]
Clevers, H [1 ]
机构
[1] Ctr Biomed Genet, Hubrecht Lab, NL-3584 CT Utrecht, Netherlands
关键词
D O I
10.1074/jbc.M307801200
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
Genetic studies on endoderm-mesoderm specification in Caenorhabditis elegans have demonstrated a role for several Wnt cascade components as well as for a MAPK-like pathway in this process. The latter pathway includes the MAPK kinase kinase-like MOM-4/Tak1, its adaptor TAP-1/Tab1, and the MAPK-like LIT-1/Nemolike kinase. A model has been proposed in which the Tak1 kinase cascade counteracts the Wnt cascade at the level of beta-catenin/TCF phosphorylation. In this model, the signal that activates the Tak1 kinase cascade is unknown. As an alternative explanation of these genetic data, we have explored whether Tak1 is directly activated by Wnt. We find that Wnt1 stimulation results in autophosphorylation and activation of MOM-4/Tak1 in a TAP-1/Tab1-dependent fashion. Wnt1-induced Tak1 stimulation activates Nemo-like kinase, resulting in the phosphorylation of TCF. Our results combined with the genetic data from C. elegans imply a mechanism whereby Wnt directly activates the MOM-4/Tak1 kinase signaling pathway. Thus, Wnt signal transduction through the canonical pathway activates beta-catenin/TCF, whereas Wnt signal transduction through the Tak1 pathway phosphorylates and inhibits TCF, which might function as a feedback mechanism.
引用
收藏
页码:17232 / 17240
页数:9
相关论文
共 49 条
[1]   A new member of the frizzled family from Drosophila functions as a Wingless receptor [J].
Bhanot, P ;
Brink, M ;
Samos, CH ;
Hsieh, JC ;
Wang, YS ;
Macke, JP ;
Andrew, D ;
Nathans, J ;
Nusse, R .
NATURE, 1996, 382 (6588) :225-230
[2]   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
[3]   Nlk is a murine protein kinase related to Erk/MAP kinases and localized in the nucleus [J].
Brott, BK ;
Pinsky, BA ;
Erikson, RL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (03) :963-968
[4]   Wnt signaling: a common theme in animal development [J].
Cadigan, KM ;
Nusse, R .
GENES & DEVELOPMENT, 1997, 11 (24) :3286-3305
[5]   A POP-1 repressor complex restricts inappropriate cell type-specific gene transcription during Caenorhabditis elegans embryogenesis [J].
Calvo, D ;
Victor, M ;
Gay, F ;
Sui, G ;
Luke, MPS ;
Dufourcq, P ;
Wen, GY ;
Maduro, M ;
Rothman, J ;
Shi, Y .
EMBO JOURNAL, 2001, 20 (24) :7197-7208
[6]   The human frizzled 6 (HFz6) acts as a negative regulator of the canonical Wnt•β-Catenin signaling cascade [J].
Golan, T ;
Yaniv, A ;
Bafico, A ;
Liu, GZ ;
Gazit, A .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (15) :14879-14888
[7]   INDUCTION OF GUT IN CAENORHABDITIS-ELEGANS EMBRYOS [J].
GOLDSTEIN, B .
NATURE, 1992, 357 (6375) :255-257
[8]  
GOLDSTEIN B, 1993, DEVELOPMENT, V121, P1221
[9]  
GUMBINER BM, 1997, CURR BIOL, V7, P443
[10]   Involvement of the p38 mitogen-activated protein kinase pathway in transforming growth factor-β-induced gene expression [J].
Hanafusa, H ;
Ninomiya-Tsuji, J ;
Masuyama, N ;
Nishita, M ;
Fujisawa, J ;
Shibuya, H ;
Matsumoto, K ;
Nishida, E .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (38) :27161-27167