| In vivo functions of the proprotein convertase PC5/6 during mouse development: Gdf11 is a likely substrate. | |
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MedLine Citation:
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PMID: 18378898 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Rachid Essalmani; Ahmed Zaid; Jadwiga Marcinkiewicz; Ann Chamberland; Antonella Pasquato; Nabil G Seidah; Annik Prat |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-03-31 |
Journal Detail:
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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:
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Created Date: 2008-04-17 Completed Date: 2008-06-13 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 5750-5 Citation Subset: IM |
Affiliation:
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Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, QC, Canada. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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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