Linked Life Data

8218226

Source:http://linkedlifedata.com/resource/pubmed/id/8218226

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
43
pubmed:dateCreated
1993-11-29
pubmed:abstractText
Proteins that transit the constitutive pathway of secretion frequently require proteolytic processing after a pair of basic amino acids to attain their full functional activity. A ubiquitously expressed calcium-dependent subtilisin-like serine protease, named PACE or furin, can cleave precursor polypeptides specifically at pairs of basic amino acids where an arginine residue is present in the P4 position. Another member of this protease family, PACE4, was cloned recently by a PCR-based strategy and was also shown to be ubiquitously expressed. We have expressed PACE4 by transient DNA transfection of COS-1 cells and have shown that the cDNA encodes a 120-kDa polypeptide that is present in cell extracts but not in conditioned medium of transfected cells. The substrate specificities of PACE and PACE4 for cleavage of pro-von Willebrand factor were studied in parallel using a transient DNA cotransfection system. Like PACE, PACE4 was able to process pro-vWF to its mature form, and efficient cleavage required both the P4 arginine and the P2 lysine. These data, taken together with previously published data showing that PACE4 cannot process pro-factor IX, demonstrate that PACE and PACE4 have overlapping but not identical substrate specificities. Further differences between PACE and PACE4 specificities were elucidated by monitoring inhibition of processing activity mediated by the serine protease inhibitor alpha 1-antitrypsin Pittsburgh mutant. Pro-vWF processing by PACE was inhibited by expression of the alpha 1-antitrypsin Pittsburgh mutant, whereas processing of pro-vWF by PACE4 was not affected.(ABSTRACT TRUNCATED AT 250 WORDS)
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
2
pubmed:volume
32
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
11586-90
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
PACE4 is a member of the mammalian propeptidase family that has overlapping but not identical substrate specificity to PACE.
pubmed:affiliation
Department of Molecular and Cellular Genetics, Genetics Institute, Cambridge, Massachusetts 02148.
pubmed:publicationType
Journal Article, Comparative Study