Specificity, diversity, and regulation in TGF-β superfamily signaling

被引:700
作者
Piek, E [1 ]
Heldin, CH [1 ]
Ten Dijke, P [1 ]
机构
[1] Ludwig Inst Canc Res, S-75124 Uppsala, Sweden
关键词
activin; bone; morphogenetic protein; signal transduction; Smad; transforming growth factor-beta;
D O I
10.1096/fasebj.13.15.2105
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
Transforming growth factor-beta (TGF-beta) superfamily members are multifunctional cell-cell signaling proteins that play pivotal roles in tissue homeostasis and development of multicellular animals, They mediate their pleiotropic effects from membrane to nucleus through distinct combinations of type I and type II serine/threonine kinase receptors and their downstream effecters, known as Smad proteins. Certain Smads, termed receptor-regulated Smads, become phosphorylated by activated type I receptors and form heteromeric complexes with a common-partner Smad4, which translocates into the nucleus to control gene transcription, In addition to these signal transducing Smads, inhibitory Smads have been identified that inhibit the activation of receptor-regulated Smads, In contrast to the still growing TGF-beta superfamily (with similar to 30 members in mammals), relatively few type I and type II receptors as well as Smads have been identified. We will focus on recent insights into the molecular mechanisms by which signaling specificity between different TGF-beta superfamily members is achieved and regulated, and how a single family member can elicit a broad scala of biological responses.
引用
收藏
页码:2105 / 2124
页数:20
相关论文
共 231 条
[1]   T beta RI phosphorylation of Smad2 on Ser(465) and Ser(467) is required for Smad2-Smad4 complex formation and signaling [J].
Abdollah, S ;
MaciasSilva, M ;
Tsukazaki, T ;
Hayashi, H ;
Attisano, L ;
Wrana, JL .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (44) :27678-27685
[2]   TRANSFORMING GROWTH FACTOR-BETA-1 (TGF-BETA-1) REDUCES CELLULAR-LEVELS OF P34CDC2, AND THIS EFFECT IS ABROGATED BY ADENOVIRUS INDEPENDENTLY OF THE E1A-ASSOCIATED PRB BINDING-ACTIVITY [J].
ABRAHAM, SE ;
CARTER, MC ;
MORAN, E .
MOLECULAR BIOLOGY OF THE CELL, 1992, 3 (06) :655-665
[3]   Induction of inhibitory Smad6 and Smad7 mRNA by TGF-β family members [J].
Afrakhte, M ;
Morén, A ;
Jossan, S ;
Itoh, S ;
Westermark, B ;
Heldin, CH ;
Heldin, NE ;
ten Dijke, P .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1998, 249 (02) :505-511
[4]   Distinct endocytic responses of heteromeric and homomeric transforming growth factor beta receptors [J].
Anders, RA ;
Arline, SL ;
Dore, JJE ;
Leof, EB .
MOLECULAR BIOLOGY OF THE CELL, 1997, 8 (11) :2133-2143
[5]   Differential requirement for type I and type II transforming growth factor β receptor kinase activity in ligand-mediated receptor endocytosis [J].
Anders, RA ;
Dore, JE ;
Arline, SL ;
Garamszegi, N ;
Leof, EB .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (36) :23118-23125
[6]   Structural basis for the pathophysiology of lipoprotein(a) in the athero-thrombotic process [J].
AnglesCano, E .
BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH, 1997, 30 (11) :1271-1280
[7]   Evidence for a role of Rho-like GTPases and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in transforming growth factor beta-mediated signaling [J].
Atfi, A ;
Djelloul, S ;
Chastre, E ;
Davis, RR ;
Gespach, C .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (03) :1429-1432
[8]   Induction of apoptosis by DPC4, a transcriptional factor regulated by transforming growth factor-beta through stress-activated protein kinase c-Jun N-terminal kinase (SAPK/JNK) signaling pathway [J].
Atfi, A ;
Buisine, M ;
Mazars, A ;
Gespach, C .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (40) :24731-24734
[9]   NOVEL ACTIVIN RECEPTORS - DISTINCT GENES AND ALTERNATIVE MESSENGER-RNA SPLICING GENERATE A REPERTOIRE OF SERINE THREONINE KINASE RECEPTORS [J].
ATTISANO, L ;
WRANA, JL ;
CHEIFETZ, S ;
MASSAGUE, J .
CELL, 1992, 68 (01) :97-108
[10]   IDENTIFICATION OF HUMAN ACTIVIN AND TGF-BETA TYPE-I RECEPTORS THAT FORM HETEROMERIC KINASE COMPLEXES WITH TYPE-II RECEPTORS [J].
ATTISANO, L ;
CARCAMO, J ;
VENTURA, F ;
WEIS, FMB ;
MASSAGUE, J ;
WRANA, JL .
CELL, 1993, 75 (04) :671-680