Source:http://linkedlifedata.com/resource/pubmed/id/16805830
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
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| pubmed:dateCreated |
2006-6-29
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| pubmed:abstractText |
The brain-specific protein p42IP4, also called centaurin-alpha1, specifically binds phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P3] and inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4]. Here, we investigate the interaction of p42IP4/centaurin-alpha1 with nardilysin (NRDc), a member of the M16 family of zinc metalloendopeptidases. Members of this peptidase family exhibit enzymatic activity and also act as receptors for other proteins. We found that p42IP4/centaurin-alpha1 binds specifically to NRDc from rat brain. We further detected that centaurin-alpha2, a protein that is highly homologous to p42IP4/centaurin-alpha1 and expressed ubiquitously, also binds to NRDc. In vivo interaction was demonstrated by co-immunoprecipitation of p42IP4/centaurin-alpha1 with NRDc from rat brain. The acidic domain of NRDc (NRDc-AD), which does not participate in catalysis, is sufficient for the protein interaction with p42IP4. Interestingly, preincubation of p42IP4 with its cognate ligands D-Ins(1,3,4,5)P4 and the lipid diC8PtdIns(3,4,5)P3 negatively modulates the interaction between the two proteins. D-Ins(1,3,4,5)P4 and diC8PtdIns(3,4,5)P3 suppress the interaction with virtually identical concentration dependencies. This inhibition is highly ligand specific. The enantiomer L-Ins(1,3,4,5)P4 is not effective. Similarly, the phosphoinositides diC8PtdIns(3,4)P2, diC8PtdIns(3,5)P2 and diC8PtdIns(4,5)P2 all have no influence on the interaction. Further experiments revealed that endogenous p42IP4 from rat brain binds to glutathione-S-transferase (GST)-NRDc-AD. The proteins dissociate from each other when incubated with D-Ins(1,3,4,5)P4, but not with inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]. In summary, we demonstrate that p42IP4 binds to NRDc via the NRDc-AD, and that this interaction is controlled by the cognate cellular ligands of p42IP4/centaurin-alpha1. Thus, specific ligands of p42IP4 can modulate the recruitment of proteins, which are docked to p42IP4, to specific cellular compartments.
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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/ADAP1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Transferase,
http://linkedlifedata.com/resource/pubmed/chemical/Inositol Phosphates,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Metalloendopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol Phosphates,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/inositol-1,3,4,5-tetrakisphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/nardilysin,
http://linkedlifedata.com/resource/pubmed/chemical/phosphatidylinositol...
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jul
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| pubmed:issn |
0022-3042
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
98
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
343-54
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| pubmed:dateRevised |
2011-9-28
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| pubmed:meshHeading |
pubmed-meshheading:16805830-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:16805830-Animals,
pubmed-meshheading:16805830-Blotting, Western,
pubmed-meshheading:16805830-Brain Chemistry,
pubmed-meshheading:16805830-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:16805830-Glutathione Transferase,
pubmed-meshheading:16805830-Humans,
pubmed-meshheading:16805830-Immunoprecipitation,
pubmed-meshheading:16805830-Inositol Phosphates,
pubmed-meshheading:16805830-Ligands,
pubmed-meshheading:16805830-Metalloendopeptidases,
pubmed-meshheading:16805830-Nerve Tissue Proteins,
pubmed-meshheading:16805830-Phosphatidylinositol Phosphates,
pubmed-meshheading:16805830-Protein Binding,
pubmed-meshheading:16805830-Rats,
pubmed-meshheading:16805830-Recombinant Fusion Proteins,
pubmed-meshheading:16805830-Stereoisomerism
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| pubmed:year |
2006
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| pubmed:articleTitle |
Interaction of the brain-specific protein p42IP4/centaurin-alpha1 with the peptidase nardilysin is regulated by the cognate ligands of p42IP4, PtdIns(3,4,5)P3 and Ins(1,3,4,5)P4, with stereospecificity.
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| pubmed:affiliation |
Institut für Neurobiochemie, Medizinische Fakultät der Otto-von-Guericke-Universität Magdeburg, Magdeburg, Germany.
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| pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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