rdf:type |
|
lifeskim:mentions |
umls-concept:C0031307,
umls-concept:C0068355,
umls-concept:C0205369,
umls-concept:C1334043,
umls-concept:C1417608,
umls-concept:C1514562,
umls-concept:C1514873,
umls-concept:C1546857,
umls-concept:C1556066,
umls-concept:C1619636,
umls-concept:C1704675,
umls-concept:C1706853,
umls-concept:C1879547,
umls-concept:C1879748,
umls-concept:C1880389,
umls-concept:C1883204,
umls-concept:C1883221,
umls-concept:C2697616
|
pubmed:issue |
36
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pubmed:dateCreated |
1996-10-10
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pubmed:abstractText |
The phagocyte NADPH oxidase is activated during phagocytosis to produce superoxide, a precursor of microbicidal oxidants. The activation involves assembly of membrane-integrated cytochrome b558 comprising gp91(phox) and p22(phox), two specialized cytosolic proteins (p47(phox) and p67(phox)), each containing two Src homology 3 (SH3) domains, and the small G protein Rac. In the present study, we show that the N-terminal SH3 domain of p47(phox) binds to the C-terminal cytoplasmic tail of p22(phox) with high affinity (KD = 0.34 microM). The binding is specific to this domain among several SH3 domains including the C-terminal one of p47(phox) and the two of p67(phox) and requires the Pro156-containing proline-rich sequence but not other putative SH3 domain-binding sites of p22(phox). Replacement of Trp193 by Arg in the N-terminal SH3 domain completely abrogates the association with p22(phox). A mutant p47(phox) with this substitution is incapable of supporting superoxide production under cell-free activation conditions. These findings provide direct evidence that the interaction between the N-terminal SH3 domain of p47(phox) and the proline-rich region of p22(phox) is essential for activation of the NADPH oxidase.
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pubmed:language |
eng
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pubmed:journal |
|
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CYBA protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome b Group,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Transport Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/NADH, NADPH Oxidoreductases,
http://linkedlifedata.com/resource/pubmed/chemical/NADPH Dehydrogenase,
http://linkedlifedata.com/resource/pubmed/chemical/NADPH Oxidase,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/cytochrome b558,
http://linkedlifedata.com/resource/pubmed/chemical/neutrophil cytosolic factor 1
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0021-9258
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pubmed:author |
|
pubmed:issnType |
Print
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pubmed:day |
6
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pubmed:volume |
271
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
22152-8
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:8703027-Cytochrome b Group,
pubmed-meshheading:8703027-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:8703027-Enzyme Activation,
pubmed-meshheading:8703027-Humans,
pubmed-meshheading:8703027-Kinetics,
pubmed-meshheading:8703027-Membrane Transport Proteins,
pubmed-meshheading:8703027-NADH, NADPH Oxidoreductases,
pubmed-meshheading:8703027-NADPH Dehydrogenase,
pubmed-meshheading:8703027-NADPH Oxidase,
pubmed-meshheading:8703027-Phagocytes,
pubmed-meshheading:8703027-Phosphoproteins,
pubmed-meshheading:8703027-Point Mutation,
pubmed-meshheading:8703027-Recombinant Fusion Proteins,
pubmed-meshheading:8703027-Structure-Activity Relationship
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pubmed:year |
1996
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pubmed:articleTitle |
Assembly and activation of the phagocyte NADPH oxidase. Specific interaction of the N-terminal Src homology 3 domain of p47phox with p22phox is required for activation of the NADPH oxidase.
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pubmed:affiliation |
Department of Biochemistry, Kyushu University School of Medicine, Fukuoka 812, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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