Linked Life Data

10477300

Source:http://linkedlifedata.com/resource/pubmed/id/10477300

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
1999-11-4
pubmed:abstractText
The Hedgehog signal transduction pathway is involved in diverse patterning events in many organisms. In Drosophila, Hedgehog signaling regulates transcription of target genes by modifying the activity of the DNA-binding protein Cubitus interruptus (Ci). Hedgehog signaling inhibits proteolytic cleavage of full-length Ci (Ci-155) to Ci-75, a form that represses some target genes, and also converts the full-length form to a potent transcriptional activator. Reduction of protein kinase A (PKA) activity also leads to accumulation of full-length Ci and to ectopic expression of Hedgehog target genes, prompting the hypothesis that PKA might normally promote cleavage to Ci-75 by directly phosphorylating Ci-155. Here we show that a mutant form of Ci lacking five potential PKA phosphorylation sites (Ci5m) is not detectably cleaved to Ci-75 in Drosophila embryos. Moreover, changes in PKA activity dramatically altered levels of full-length wild-type Ci in embryos and imaginal discs, but did not significantly alter full-length Ci5m levels. We corroborate these results by showing that Ci5m is more active than wild-type Ci at inducing ectopic transcription of the Hh target gene wingless in embryos and that inhibition of PKA enhances induction of wingless by wild-type Ci but not by Ci5m. We therefore propose that PKA phosphorylation of Ci is required for the proteolysis of Ci-155 to Ci-75 in vivo. We also show that the activity of Ci5m remains Hedgehog responsive if expressed at low levels, providing further evidence that the full-length form of Ci undergoes a Hedgehog-dependent activation step.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0950-1991
pubmed:author
pubmed:issnType
Print
pubmed:volume
126
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4331-9
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:10477300-Amino Acid Sequence, pubmed-meshheading:10477300-Animals, pubmed-meshheading:10477300-Animals, Genetically Modified, pubmed-meshheading:10477300-Cyclic AMP-Dependent Protein Kinases, pubmed-meshheading:10477300-DNA-Binding Proteins, pubmed-meshheading:10477300-Drosophila, pubmed-meshheading:10477300-Drosophila Proteins, pubmed-meshheading:10477300-Embryo, Nonmammalian, pubmed-meshheading:10477300-Hedgehog Proteins, pubmed-meshheading:10477300-Insect Proteins, pubmed-meshheading:10477300-Models, Genetic, pubmed-meshheading:10477300-Molecular Sequence Data, pubmed-meshheading:10477300-Mutagenesis, pubmed-meshheading:10477300-Phosphorylation, pubmed-meshheading:10477300-Recombinant Proteins, pubmed-meshheading:10477300-Sequence Homology, Amino Acid, pubmed-meshheading:10477300-Transcription, Genetic, pubmed-meshheading:10477300-Transcription Factors, pubmed-meshheading:10477300-Wing
pubmed:year
1999
pubmed:articleTitle
Proteolysis of cubitus interruptus in Drosophila requires phosphorylation by protein kinase A.
pubmed:affiliation
Department of Biological Sciences, Columbia University, New York, New York 10027, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.