Document Detail


In vivo functions of the proprotein convertase PC5/6 during mouse development: Gdf11 is a likely substrate.
MedLine Citation:
PMID:  18378898     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The proprotein convertase PC5/6 cleaves protein precursors after basic amino acids and is essential for implantation in CD1/129/Sv/C57BL/6 mixed-background mice. Conditional inactivation of Pcsk5 in the epiblast but not in the extraembryonic tissue bypassed early embryonic lethality but resulted in death at birth. PC5/6-deficient embryos exhibited Gdf11-related phenotypes such as altered anteroposterior patterning with extra vertebrae and lack of tail and kidney agenesis. They also exhibited Gdf11-independent phenotypes, such as a smaller size, multiple hemorrhages, collapsed alveoli, and retarded ossification. In situ hybridization revealed overlapping PC5/6 and Gdf11 mRNA expression patterns. In vitro and ex vivo analyses showed that the selectivity of PC5/6 for Gdf11 essentially resides in the presence of a P1' Asn in the RSRR downward arrowN cleavage motif. This work identifies Gdf11 as a likely in vivo specific substrate of PC5/6 and opens the way to the identification of other key substrates of this convertase.
Authors:
Rachid Essalmani; Ahmed Zaid; Jadwiga Marcinkiewicz; Ann Chamberland; Antonella Pasquato; Nabil G Seidah; Annik Prat
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-03-31
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  105     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2008 Apr 
Date Detail:
Created Date:  2008-04-17     Completed Date:  2008-06-13     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5750-5     Citation Subset:  IM    
Affiliation:
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, QC, Canada.
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MeSH Terms
Descriptor/Qualifier:
Animals
Bone Morphogenetic Proteins / genetics,  metabolism,  physiology*
Growth Differentiation Factors
Growth and Development*
Mice
Phenotype
Proprotein Convertase 5 / genetics,  metabolism,  physiology*
RNA, Messenger / analysis
Substrate Specificity
Chemical
Reg. No./Substance:
0/Bone Morphogenetic Proteins; 0/Gdf11 protein, mouse; 0/Growth Differentiation Factors; 0/RNA, Messenger; EC 3.4.21.-/Proprotein Convertase 5; EC 3.4.21.-/propeptide convertase 5, mouse
Comments/Corrections

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