PUBLICATION
Homologues of Twisted gastrulation are extracellular cofactors in antagonism of BMP signalling
- Authors
- Scott, I.C., Blitz, I.L., Pappano, W.N., Maas, S.A., Cho, K.W., and Greenspan, D.S.
- ID
- ZDB-PUB-010405-2
- Date
- 2001
- Source
- Nature 410(6827): 475-478 (Journal)
- Registered Authors
- Blitz, Ira
- Keywords
- none
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Bone Morphogenetic Protein 4
- Bone Morphogenetic Proteins/antagonists & inhibitors
- Bone Morphogenetic Proteins/metabolism*
- Chick Embryo
- Chromosome Mapping
- Chromosomes, Human, Pair 18
- Drosophila Proteins*
- Gastrula/metabolism*
- Gene Expression Profiling
- Glycoproteins*
- Humans
- Intercellular Signaling Peptides and Proteins*
- Mice
- Molecular Sequence Data
- Peptide Fragments/metabolism
- Protein Binding
- Proteins/chemistry
- Proteins/genetics
- Proteins/metabolism*
- Proteins/physiology*
- Recombinant Proteins/metabolism
- Signal Transduction*
- Xenopus
- Xenopus Proteins
- Zebrafish
- Zebrafish Proteins
- PubMed
- 11260715 Full text @ Nature
Citation
Scott, I.C., Blitz, I.L., Pappano, W.N., Maas, S.A., Cho, K.W., and Greenspan, D.S. (2001) Homologues of Twisted gastrulation are extracellular cofactors in antagonism of BMP signalling. Nature. 410(6827):475-478.
Abstract
Twisted gastrulation (TSG) is involved in specifying the dorsal-most cell fate in Drosophila embryos, but its mechanism of action is poorly understood. TSG has been proposed to modify the action of Short gastrulation (SOG), thereby increasing signalling by the bone morphogenetic protein (BMP) Decapentaplegic. SOG, an inhibitor of BMP signalling, is in turn inactivated by the protease Tolloid. Here we identify Tsg gene products from human, mouse, Xenopus, zebrafish and chick. Expression patterns in mouse and Xenopus embryos are consistent with in vivo interactions between Tsg, BMPs and the vertebrate SOG orthologue, chordin. We show that Tsg binds both the vertebrate Decapentaplegic orthologue BMP4 and chordin, and that these interactions have multiple effects. Tsg increases chordin's binding of BMP4, potentiates chordin's ability to induce secondary axes in Xenopus embryos, and enhances chordin cleavage by vertebrate tolloid-related proteases at a site poorly used in Tsg's absence; also, the presence of Tsg enhances the secondary axis-inducing activity of two products of chordin cleavage. We conclude that Tsg acts as a cofactor in chordin's antagonism of BMP signalling.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping