Linked Life Data

21288900

Source:http://linkedlifedata.com/resource/pubmed/id/21288900

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2011-4-1
pubmed:abstractText
Corin is a cardiac membrane protease that activates natriuretic peptides. It is unknown how corin function is regulated. Recently, soluble corin was detected in human plasma, suggesting that corin may be shed from cardiomyocytes. Here we examined soluble corin production and activity and determined the proteolytic enzymes responsible for corin cleavage. We expressed human corin in HEK 293 cells and detected three soluble fragments of ?180, ?160, and ?100 kDa, respectively, in the cultured medium by Western blot analysis. All three fragments were derived from activated corin molecules. Similar results were obtained in HL-1 cardiomyocytes. Using protease inhibitors, ionomycin and phorbol myristate acetate stimulation, small interfering RNA knockdown, and site-directed mutagenesis, we found that ADAM10 was primarily responsible for shedding corin in its juxtamembrane region to release the ?180-kDa fragment, corresponding to the near-entire extracellular region. In contrast, the ?160- and ?100-kDa fragments were from corin autocleavage at Arg-164 in frizzled 1 domain and Arg-427 in LDL receptor 5 domain, respectively. In functional studies, the ?180-kDa fragment activated atrial natriuretic peptide, whereas the ?160- and ?100-kDa fragments did not. Our data indicate that ADAM-mediated shedding and corin autocleavage are important mechanisms regulating corin function and preventing excessive, potentially hazardous, proteolytic activities in the heart.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1083-351X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
25
pubmed:volume
286
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
10066-72
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Ectodomain shedding and autocleavage of the cardiac membrane protease corin.
pubmed:affiliation
Department of Molecular Cardiology, Nephrology, and Hypertension, Cleveland Clinic, Cleveland, Ohio 44195, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural