ATF-2 is a common nuclear target of Smad and TAK1 pathways in transforming growth factor-β signaling

被引:303
作者
Sano, Y
Harada, J
Tashiro, S
Gotoh-Mandeville, R
Maekawa, T
Ishii, S
机构
[1] RIKEN, Tsukuba Life Sci Ctr, Mol Genet Lab, Ibaraki, Osaka 3050074, Japan
[2] Japan Sci & Technol Corp, Core Res Evolut Sci & Technol, Osaka, Japan
关键词
D O I
10.1074/jbc.274.13.8949
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
Upon transforming growth factor-beta (TGF-beta) binding to its cognate receptor, Smad3 and Smad4 form heterodimers and transduce the TGF-beta signal to the nucleus. In addition to the Smad pathway, another pathway involving a member of the mitogen-activated protein kinase kinase kinase family of kinases, TGF-beta-activated kinase-1 (TAK1), is required for TGF-beta signaling. However, it is unknown how these pathways function together to synergistically amplify TGF-beta signaling. Here we report that the transcription factor ATF-2 (also called CRE-BP1) is bound by a hetero-oligomer of Smad3 and Smad4 upon TGF-beta stimulation. ATF-2 is one member of the ATF/CREB family that binds to the cAMP response element, and its activity is enhanced after phosphorylation by stress-activated protein kinases such as c-Jun N-terminal kinase and p38. The binding between ATF-2 and Smad3/4 is mediated via the MH1 region of the Smad proteins and the basic leucine zipper region of ATF-2. TGF-beta signaling also induces the phosphorylation of ATF-2 via TAK1 and p38. Both of these actions are shown to be responsible for the synergistic stimulation of ATF-2 trans-activating capacity. These results indicate that ATF-2 plays a central role in TGF-beta signaling by acting as a common nuclear target of both Smad and TAK1 pathways.
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收藏
页码:8949 / 8957
页数:9
相关论文
共 65 条
[11]   INDEPENDENT HUMAN MAP KINASE SIGNAL-TRANSDUCTION PATHWAYS DEFINED BY MEK AND MKK ISOFORMS [J].
DERIJARD, B ;
RAINGEAUD, J ;
BARRETT, T ;
WU, IH ;
HAN, JH ;
ULEVITCH, RJ ;
DAVIS, RJ .
SCIENCE, 1995, 267 (5198) :682-685
[12]   MADR2 maps to 18q21 and encodes a TGF beta-regulated MAD-related protein that is functionally mutated in colorectal carcinoma [J].
Eppert, K ;
Scherer, SW ;
Ozcelik, H ;
Pirone, R ;
Hoodless, P ;
Kim, H ;
Tsui, LC ;
Bapat, B ;
Gallinger, S ;
Andrulis, IL ;
Thomsen, GH ;
Wrana, JL ;
Attisano, L .
CELL, 1996, 86 (04) :543-552
[13]   A CREB-binding site as a target for decapentaplegic signalling during Drosophila endoderm induction [J].
Eresh, S ;
Riese, J ;
Jackson, DB ;
Bohmann, D ;
Bienz, M .
EMBO JOURNAL, 1997, 16 (08) :2014-2022
[14]   INTERLEUKIN-1 ACTIVATES A NOVEL PROTEIN-KINASE CASCADE THAT RESULTS IN THE PHOSPHORYLATION OF HSP27 [J].
FRESHNEY, NW ;
RAWLINSON, L ;
GUESDON, F ;
JONES, E ;
COWLEY, S ;
HSUAN, J ;
SAKLATVALA, J .
CELL, 1994, 78 (06) :1039-1049
[15]   ISOLATION AND CHARACTERIZATION OF 2 NOVEL, CLOSELY RELATED ATF CDNA CLONES FROM HELA-CELLS [J].
GAIRE, M ;
CHATTON, B ;
KEDINGER, C .
NUCLEIC ACIDS RESEARCH, 1990, 18 (12) :3467-3473
[16]   A CLUSTER OF PHOSPHORYLATION SITES ON THE CYCLIC AMP-REGULATED NUCLEAR FACTOR CREB PREDICTED BY ITS SEQUENCE [J].
GONZALEZ, GA ;
YAMAMOTO, KK ;
FISCHER, WH ;
KARR, D ;
MENZEL, P ;
BIGGS, W ;
VALE, WW ;
MONTMINY, MR .
NATURE, 1989, 337 (6209) :749-752
[17]   CYCLIC-AMP STIMULATES SOMATOSTATIN GENE-TRANSCRIPTION BY PHOSPHORYLATION OF CREB AT SERINE-133 [J].
GONZALEZ, GA ;
MONTMINY, MR .
CELL, 1989, 59 (04) :675-680
[18]   Xenopus Mad proteins transduce distinct subsets of signals for the TGF beta superfamily [J].
Graff, JM ;
Bansal, A ;
Melton, DA .
CELL, 1996, 85 (04) :479-487
[19]   TRANSCRIPTION FACTOR ATF2 REGULATION BY THE JNK SIGNAL-TRANSDUCTION PATHWAY [J].
GUPTA, S ;
CAMPBELL, D ;
DERIJARD, B ;
DAVIS, RJ .
SCIENCE, 1995, 267 (5196) :389-393
[20]   CROSS-FAMILY DIMERIZATION OF TRANSCRIPTION FACTORS FOS JUN AND ATF CREB ALTERS DNA-BINDING SPECIFICITY [J].
HAI, T ;
CURRAN, T .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (09) :3720-3724