Document Detail


Xenopus ADAMTS1 negatively modulates FGF signaling independent of its metalloprotease activity.
MedLine Citation:
PMID:  16690049     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We have isolated the Xenopus ortholog of ADAMTS1 (a disintegrin and metalloprotease with thrombospondin motifs), XADAMTS1, which is expressed in the presumptive ectoderm, then the Spemann organizer, and later in the trunk organizer region and posterior ectoderm in the Xenopus embryo. We show that, when overexpressed in the dorsal marginal zone or in the anterior ectoderm by mRNA injection, XADAMTS1 inhibits gastrulation or generates embryos with an enlarged cement gland, respectively. XADAMTS1 also reduces the expression of Xbra in both whole embryos and FGF-treated animal caps. These effects of XADAMTS1 are likely to be due to its inhibition of the Ras-MAPK cascade because XADAMTS1 inhibits the phosphorylation of ERK by FGF4 in animal caps. Deletion analysis of XADAMTS1 revealed that a combination of the signal peptide and the C-terminal region containing the thrombospondin type 1 repeats is necessary and sufficient for this function, whereas the metalloprotease domain is dispensable. In addition, loss-of-function analysis with antisense morpholino oligos showed that knockdown of XADAMTS1 sensitizes animal caps to Xbra induction by FGF2. These data suggest that secreted XADAMTS1 negatively modulates FGF signaling in the Xenopus embryo.
Authors:
Akiko Suga; Hiroki Hikasa; Masanori Taira
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-05-09
Journal Detail:
Title:  Developmental biology     Volume:  295     ISSN:  0012-1606     ISO Abbreviation:  Dev. Biol.     Publication Date:  2006 Jul 
Date Detail:
Created Date:  2006-07-10     Completed Date:  2006-08-30     Revised Date:  2010-10-08    
Medline Journal Info:
Nlm Unique ID:  0372762     Medline TA:  Dev Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  26-39     Citation Subset:  IM    
Affiliation:
Department of Biological Sciences, Graduate School of Science, University of Tokyo, Japan.
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MeSH Terms
Descriptor/Qualifier:
ADAM Proteins / genetics,  metabolism*
Amino Acid Sequence
Animals
Cloning, Molecular
Ectoderm / metabolism
Embryo, Nonmammalian / drug effects
Fibroblast Growth Factor 2 / metabolism,  pharmacology
Fibroblast Growth Factors / metabolism*
Gastrula / metabolism
Gene Expression Regulation, Developmental*
Heparin / metabolism
Mesoderm / metabolism
Metalloproteases / metabolism
Molecular Sequence Data
Protein Structure, Tertiary
Signal Transduction*
T-Box Domain Proteins / genetics,  metabolism
Xenopus / embryology,  metabolism*
Xenopus Proteins / genetics,  metabolism*
Chemical
Reg. No./Substance:
0/T-Box Domain Proteins; 0/Xbra protein, Xenopus; 0/Xenopus Proteins; 103107-01-3/Fibroblast Growth Factor 2; 62031-54-3/Fibroblast Growth Factors; 9005-49-6/Heparin; EC 3.4.-/Metalloproteases; EC 3.4.24.-/ADAM Proteins; EC 3.4.24.-/ADAMTS1 protein, Xenopus

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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