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PMID: 9679059 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Determinants of specificity in TGF-beta signal transduction.

Genes & development ·Vol. 12 ·No. 14 ·1998-07-15 ·Pages 2144-52

Chen YG, Hata A, Lo RS, Wotton D, Shi Y, Pavletich N, Massagué J

Abstract

Signal transduction by the TGF-beta family involves sets of receptor serine/threonine kinases, Smad proteins that act as receptor substrates, and Smad-associated transcription factors that target specific genes. We have identified discrete structural elements that dictate the selective interactions between receptors and Smads and between Smads and transcription factors in the TGF-beta and BMP pathways. A cluster of four residues in the L45 loop of the type I receptor kinase domain, and a matching set of two residues in the L3 loop of the Smad carboxy-terminal domain establish the specificity of receptor-Smad interactions. A cluster of residues in the highly exposed alpha-helix 2 of the Smad carboxy-terminal domain specify the interaction with the DNA-binding factor Fast1 and, as a result, the gene responses mediated by the pathway. By establishing specific interactions, these determinants keep the TGF-beta and BMP pathways segregated from each other.

MeSH Terms
Activin Receptors, Type I Amino Acid Sequence Animals Binding Sites COS Cells DNA-Binding Proteins/metabolism Forkhead Transcription Factors Humans Molecular Sequence Data Protein Serine-Threonine Kinases/genetics,metabolism,physiology Receptor, Transforming Growth Factor-beta Type I Receptors, Transforming Growth Factor beta/genetics,metabolism,physiology Signal Transduction Smad Proteins Smad2 Protein Smad3 Protein Trans-Activators Transcription Factors/metabolism Transforming Growth Factor beta/metabolism Tumor Cells, Cultured Xenopus Xenopus Proteins
Chemicals
DNA-Binding Proteins FOXH1 protein, Xenopus FOXH1 protein, human Forkhead Transcription Factors Foxh1 protein, mouse Receptors, Transforming Growth Factor beta SMAD2 protein, human SMAD3 protein, human Smad Proteins Smad2 Protein Smad2 protein, Xenopus Smad3 Protein Trans-Activators Transcription Factors Transforming Growth Factor beta Xenopus Proteins Protein Serine-Threonine Kinases Activin Receptors, Type I Receptor, Transforming Growth Factor-beta Type I
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Chen Y G
Cell Biology Program, Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021 USA.
Hata A
Lo R S
Wotton D
Shi Y
Pavletich N
Massagué J
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.12.14.2144
Published
1998-07-15
Pages
2144-52
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC317013
Subset
IM
External Links
PubMed source DOI: 10.1101/gad.12.14.2144 PMC Full Text View journal details
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