rdf:type |
|
lifeskim:mentions |
umls-concept:C0026336,
umls-concept:C0033640,
umls-concept:C0109317,
umls-concept:C0151650,
umls-concept:C0529196,
umls-concept:C0752312,
umls-concept:C1150579,
umls-concept:C1333340,
umls-concept:C1366882,
umls-concept:C1370600,
umls-concept:C1705767,
umls-concept:C1705791,
umls-concept:C1879547
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pubmed:issue |
2
|
pubmed:dateCreated |
2010-2-11
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pubmed:abstractText |
Chronic kidney disease affects 1 of 9 Americans. Recent studies showed increased activation of the metalloenzyme disintegrin ADAM-17 during the development of the disease and that threonine phosphorylation of ADAM-17 may be an important regulator of the enzyme activity. Using kidney mesangial cells we investigated whether profibrotic serotonin (5-HT) induces phosphorylation of ADAM-17 with concomitant increase in the enzyme activity. We found that 5-HT treatment (1 mM for 10 minutes) induced a significant 3-fold increase in ADAM-17 phosphorylation and employing a fluorogenic enzyme activity assay we showed 2.3-fold activation of ADAM-17, both of which was inhibited by PD98059 (1 mM), an inhibitor of extracellular signal regulated kinase (ERK) activation. In coimmunoprecipitation analysis, we observed increased (2.7-fold) binding of activated ERK to ADAM-17 during 5-HT stimulation. We concluded that, during profibrotic stimulus, ERK phosphorylates ADAM-17 in kidney cells which induces concomitant increase in the enzyme activity.
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pubmed:grant |
|
pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
|
pubmed:citationSubset |
AIM
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pubmed:chemical |
|
pubmed:status |
MEDLINE
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pubmed:month |
Feb
|
pubmed:issn |
1538-2990
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pubmed:author |
|
pubmed:issnType |
Electronic
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pubmed:volume |
339
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
105-7
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pubmed:dateRevised |
2011-7-22
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pubmed:meshHeading |
pubmed-meshheading:20087163-ADAM Proteins,
pubmed-meshheading:20087163-Animals,
pubmed-meshheading:20087163-Fibrosis,
pubmed-meshheading:20087163-Flavonoids,
pubmed-meshheading:20087163-Gene Expression Regulation,
pubmed-meshheading:20087163-Kidney Diseases,
pubmed-meshheading:20087163-Mesangial Cells,
pubmed-meshheading:20087163-Mitogen-Activated Protein Kinase Kinases,
pubmed-meshheading:20087163-Phosphorylation,
pubmed-meshheading:20087163-Rats,
pubmed-meshheading:20087163-Rats, Sprague-Dawley,
pubmed-meshheading:20087163-Serotonin
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pubmed:year |
2010
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pubmed:articleTitle |
ADAM-17 is activated by the mitogenic protein kinase ERK in a model of kidney fibrosis.
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pubmed:affiliation |
Medical University of South Carolina, Charleston, 29425, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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