Specificity, versatility, and control of TGF-β family signaling

被引:545
作者
Derynck, Rik [1 ]
Budi, Erine H. [1 ,2 ]
机构
[1] Univ Calif San Francisco, Dept Cell & Tissue Biol, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA
基金
美国国家卫生研究院;
关键词
GROWTH-FACTOR-BETA; BONE MORPHOGENETIC PROTEIN; EPITHELIAL-MESENCHYMAL TRANSITION; N-LINKED GLYCOSYLATION; FYVE DOMAIN PROTEIN; CRYSTAL-STRUCTURE; NUCLEAR EXPORT; SMAD PROTEINS; II RECEPTOR; TRANSFORMING GROWTH-FACTOR-BETA-1;
D O I
10.1126/scisignal.aav5183
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
Encoded in mammalian cells by 33 genes, the transforming growth factor-beta (TGF-beta) family of secreted, homodimeric and heterodimeric proteins controls the differentiation of most, if not all, cell lineages and many aspects of cell and tissue physiology in multicellular eukaryotes. Deregulation of TGF-beta family signaling leads to developmental anomalies and disease, whereas enhanced TGF-beta signaling contributes to cancer and fibrosis. Here, we review the fundamentals of the signaling mechanisms that are initiated upon TGF-beta ligand binding to its cell surface receptors and the dependence of the signaling responses on input from and cooperation with other signaling pathways. We discuss how cells exquisitely control the functional presentation and activation of heteromeric receptor complexes of transmembrane, dual-specificity kinases and, thus, define their context-dependent responsiveness to ligands. We also introduce the mechanisms through which proteins called Smads act as intracellular effectors of ligand-induced gene expression responses and show that the specificity and impressive versatility of Smad signaling depend on cross-talk from other pathways. Last, we discuss how non-Smad signaling mechanisms, initiated by distinct ligand-activated receptor complexes, complement Smad signaling and thus contribute to cellular responses.
引用
收藏
页数:24
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共 344 条
[1]   Recruitment of TIF1γ to Chromatin via Its PHD Finger-Bromodomain Activates Its Ubiquitin Ligase and Transcriptional Repressor Activities [J].
Agricola, Eleonora ;
Randall, Rebecca A. ;
Gaarenstroom, Tessa ;
Dupont, Sirio ;
Hill, Caroline S. .
MOLECULAR CELL, 2011, 43 (01) :85-96
[2]   Smad3 regulates E-cadherin via miRNA-200 pathway [J].
Ahn, S-M ;
Cha, J-Y ;
Kim, J. ;
Kim, D. ;
Trang, H. T. H. ;
Kim, Y-M ;
Cho, Y-H ;
Park, D. ;
Hong, S. .
ONCOGENE, 2012, 31 (25) :3051-3059
[3]   Evolution of the GDNF family ligands and receptors [J].
Airaksinen, Matti S. ;
Holm, Liisa ;
Hatinen, Tuomas .
BRAIN BEHAVIOR AND EVOLUTION, 2006, 68 (03) :181-190
[4]   The GDNF family: Signalling, biological functions and therapeutic value [J].
Airaksinen, MS ;
Saarma, M .
NATURE REVIEWS NEUROSCIENCE, 2002, 3 (05) :383-394
[5]   A Large Bioactive BMP Ligand with Distinct Signaling Properties Is Produced by Alternative Proconvertase Processing [J].
Akiyama, Takuya ;
Marques, Guillermo ;
Wharton, Kristi A. .
SCIENCE SIGNALING, 2012, 5 (218)
[6]   Nuclear CDKs Drive Smad Transcriptional Activation and Turnover in BMP and TGF-β Pathways [J].
Alarcon, Claudio ;
Zaromytidou, Alexia-Ileana ;
Xi, Qiaoran ;
Gao, Sheng ;
Yu, Jianzhong ;
Fujisawa, Sho ;
Barlas, Afsar ;
Miller, Alexandria N. ;
Manova-Todorova, Katia ;
Macias, Maria J. ;
Sapkota, Gopal ;
Pan, Duojia ;
Massague, Joan .
CELL, 2009, 139 (04) :757-769
[7]   Increase of O-Glycosylated Oncofetal Fibronectin in High Glucose-Induced Epithelial-Mesenchymal Transition of Cultured Human Epithelial Cells [J].
Alisson-Silva, Frederico ;
Freire-de-Lima, Leonardo ;
Donadio, Joana L. ;
Lucena, Miguel C. ;
Penha, Luciana ;
Sa-Diniz, Julliana N. ;
Dias, Wagner B. ;
Todeschini, Adriane R. .
PLOS ONE, 2013, 8 (04)
[8]   TGF-β-induced repression of CBFA1 by Smad3 decreases cbfa1 and osteocalcin expression and inhibits osteoblast differentiation [J].
Alliston, T ;
Choy, L ;
Ducy, P ;
Karsenty, G ;
Derynck, R .
EMBO JOURNAL, 2001, 20 (09) :2254-2272
[9]   Repression of bone morphogenetic protein and activin-inducible transcription by Evi-1 [J].
Alliston, T ;
Ko, TC ;
Cao, YN ;
Liang, YY ;
Feng, XH ;
Chang, CB ;
Derynck, R .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (25) :24227-24237
[10]   Alternative cleavage of the bone morphogenetic protein (BMP), Gbb, produces ligands with distinct developmental functions and receptor preferences [J].
Anderson, Edward N. ;
Wharton, Kristi A. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2017, 292 (47) :19160-19178