Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
17
pubmed:dateCreated
1999-10-28
pubmed:abstractText
The Drosophila sugarless and sulfateless genes encode enzymes required for the biosynthesis of heparan sulfate glycosaminoglycans. Biochemical studies have shown that heparan sulfate glycosaminoglycans are involved in signaling by fibroblast growth factor receptors, but evidence for such a requirement in an intact organism has not been available. We now demonstrate that sugarless and sulfateless mutant embryos have phenotypes similar to those lacking the functions of two Drosophila fibroblast growth factor receptors, Heartless and Breathless. Moreover, both Heartless- and Breathless-dependent MAPK activation is significantly reduced in embryos which fail to synthesize heparan sulfate glycosaminoglycans. Consistent with an involvement of Sulfateless and Sugarless in fibroblast growth factor receptor signaling, a constitutively activated form of Heartless partially rescues sugarless and sulfateless mutants, and dosage-sensitive interactions occur between heartless and the heparan sulfate glycosaminoglycan biosynthetic enzyme genes. We also find that overexpression of Branchless, the Breathless ligand, can partially overcome the requirement of Sugarless and Sulfateless for Breathless activity. These results provide the first genetic evidence that heparan sulfate glycosaminoglycans are essential for fibroblast growth factor receptor signaling in a well defined developmental context, and support a model in which heparan sulfate glycosaminoglycans facilitate fibroblast growth factor ligand and/or ligand-receptor oligomerization.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Amidohydrolases, http://linkedlifedata.com/resource/pubmed/chemical/Drosophila Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Fibroblast Growth Factors, http://linkedlifedata.com/resource/pubmed/chemical/Heparan Sulfate Proteoglycans, http://linkedlifedata.com/resource/pubmed/chemical/Insect Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Fibroblast Growth Factor, http://linkedlifedata.com/resource/pubmed/chemical/Sulfotransferases, http://linkedlifedata.com/resource/pubmed/chemical/branchless protein, Drosophila, http://linkedlifedata.com/resource/pubmed/chemical/breathless protein, Drosophila, http://linkedlifedata.com/resource/pubmed/chemical/heartless protein, Drosophila, http://linkedlifedata.com/resource/pubmed/chemical/heparitin sulfotransferase, http://linkedlifedata.com/resource/pubmed/chemical/sfl protein, Drosophila
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0950-1991
pubmed:author
pubmed:issnType
Print
pubmed:volume
126
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3715-23
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:10433902-Amidohydrolases, pubmed-meshheading:10433902-Animals, pubmed-meshheading:10433902-Drosophila, pubmed-meshheading:10433902-Drosophila Proteins, pubmed-meshheading:10433902-Fibroblast Growth Factors, pubmed-meshheading:10433902-Gene Expression, pubmed-meshheading:10433902-Genes, Insect, pubmed-meshheading:10433902-Heparan Sulfate Proteoglycans, pubmed-meshheading:10433902-Insect Proteins, pubmed-meshheading:10433902-Mesoderm, pubmed-meshheading:10433902-Mitogen-Activated Protein Kinases, pubmed-meshheading:10433902-Mutation, pubmed-meshheading:10433902-Phenotype, pubmed-meshheading:10433902-Protein-Tyrosine Kinases, pubmed-meshheading:10433902-Receptors, Fibroblast Growth Factor, pubmed-meshheading:10433902-Signal Transduction, pubmed-meshheading:10433902-Sulfotransferases, pubmed-meshheading:10433902-Trachea
pubmed:year
1999
pubmed:articleTitle
Heparan sulfate proteoglycans are essential for FGF receptor signaling during Drosophila embryonic development.
pubmed:affiliation
Department of Genetics and Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S.