Source:http://linkedlifedata.com/resource/pubmed/id/12933801
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
48
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| pubmed:dateCreated |
2003-11-24
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| pubmed:abstractText |
Surfactant protein C (SP-C) is a lung-specific protein that is synthesized as a 21-kDa integral membrane propeptide (pro-SP-C) and proteolytically processed to a 3.7-kDa secretory product. Previous studies have shown that palmitoylation of pro-SP-C is dependent on two N-terminal juxtamembrane positively charged residues. We hypothesized that these residues influence modification of pro-SP-C by directing transmembrane orientation. Double substitution mutation of these juxtaposed residues from positive to neutral charged species resulted in complete reversal of transmembrane orientation of pro-SP-C and total abrogation of post-translational processing. Mutation of a single residue resulted in mixed orientation. Protein trafficking studies in A549 cells showed that while the double mutant was retained in the endoplasmic reticulum, single mutants produced a mixed pattern of both endoplasmic reticulum (double mutant-like) and vesicular (wild type-like) expression. Our study demonstrates the crucial role juxtamembrane positively charged residues play in establishing membrane topology and their influence on the trafficking and processing of pro-SP-C. Moreover this study provides a likely precedent for a mechanism in disorders associated with mutations in the membrane-flanking region of integral membrane proteins.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Arginine,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Epitopes,
http://linkedlifedata.com/resource/pubmed/chemical/Green Fluorescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Luminescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Lysine,
http://linkedlifedata.com/resource/pubmed/chemical/Pulmonary Surfactant-Associated...
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| pubmed:status |
MEDLINE
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| pubmed:month |
Nov
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| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
28
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| pubmed:volume |
278
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
47979-86
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| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading |
pubmed-meshheading:12933801-Amino Acid Sequence,
pubmed-meshheading:12933801-Animals,
pubmed-meshheading:12933801-Arginine,
pubmed-meshheading:12933801-Cell Line, Tumor,
pubmed-meshheading:12933801-Cell Membrane,
pubmed-meshheading:12933801-DNA, Complementary,
pubmed-meshheading:12933801-Endopeptidases,
pubmed-meshheading:12933801-Endoplasmic Reticulum,
pubmed-meshheading:12933801-Epitopes,
pubmed-meshheading:12933801-Green Fluorescent Proteins,
pubmed-meshheading:12933801-Humans,
pubmed-meshheading:12933801-Immunoblotting,
pubmed-meshheading:12933801-Immunohistochemistry,
pubmed-meshheading:12933801-Luminescent Proteins,
pubmed-meshheading:12933801-Lysine,
pubmed-meshheading:12933801-Microscopy, Fluorescence,
pubmed-meshheading:12933801-Molecular Sequence Data,
pubmed-meshheading:12933801-Mutation,
pubmed-meshheading:12933801-Protein Structure, Tertiary,
pubmed-meshheading:12933801-Pulmonary Surfactant-Associated Protein C,
pubmed-meshheading:12933801-Rats
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| pubmed:year |
2003
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| pubmed:articleTitle |
Processing of surfactant protein C requires a type II transmembrane topology directed by juxtamembrane positively charged residues.
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| pubmed:affiliation |
Lung Epithelial Cell Biology Laboratories, Pulmonary and Critical Care Division, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-4318, USA. mulugeta@mail.med.upenn.edu
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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