Linked Life Data

11369206

Source:http://linkedlifedata.com/resource/pubmed/id/11369206

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2001-5-22
pubmed:abstractText
The tumor suppressor gene patched (ptc) encodes an approximately 140 kDa polytopic transmembrane protein [1-3] [corrected] that binds members of the Hedgehog (Hh) family of signaling proteins [4-6] [corrected] and regulates the activity of Smoothened (Smo), a G protein-coupled receptor-like protein essential for Hh signal transduction [7-9] [corrected]. Ptc contains a sterol-sensing domain (SSD) [10, 11] [corrected], a motif found in proteins implicated in the intracellular trafficking of cholesterol [12] [corrected], and/or other cargoes [13-15] [corrected]. Cholesterol plays a critical role in Hedgehog (Hh) signaling by facilitating the regulated secretion and sequestration of the Hh protein [16] [corrected], to which it is covalently coupled. In addition, cholesterol synthesis inhibitors block the ability of cells to respond to Hh [18, 19] [corrected], and this finding points to an additional requirement for the lipid in regulating downstream components of the Hh signaling pathway. Although the SSD of Ptc has been linked to both the sequestration of, and the cellular response to Hh [16, 20, 21] [corrected], definitive evidence for its function has so far been lacking. Here we describe the identification and characterization of two missense mutations in the SSD of Drosophila Ptc; strikingly, while both mutations abolish Smo repression, neither affects the ability of Ptc to interact with Hh. We speculate that Ptc may control Smo activity by regulating an intracellular trafficking process dependent upon the integrity of the SSD.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Drosophila Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Hedgehog Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Insect Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, G-Protein-Coupled, http://linkedlifedata.com/resource/pubmed/chemical/Sterols, http://linkedlifedata.com/resource/pubmed/chemical/dpp protein, Drosophila, http://linkedlifedata.com/resource/pubmed/chemical/hedgehog protein, Drosophila, http://linkedlifedata.com/resource/pubmed/chemical/ptc protein, Drosophila, http://linkedlifedata.com/resource/pubmed/chemical/smoothened protein, Drosophila
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0960-9822
pubmed:author
pubmed:issnType
Print
pubmed:day
17
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
608-13
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Mutations in the sterol-sensing domain of Patched suggest a role for vesicular trafficking in Smoothened regulation.
pubmed:affiliation
MRC Intercellular Signalling Group, Centre for Developmental Genetics, Department of Biomedical Science, University of Sheffield, Sheffield, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't