Ontogeny of prohormone convertases in rat prenatal development.
It has been well established that peptide precursors usually undergo limited proteolysis at pairs or single basic amino acids during their biosynthetic process. This posttranslational modification paradigm is common for numerous membrane-spanning and secreted proteins, neuropeptides, and peptide hormones of physiological significance, in which endoproteolytic cleavage is invariably essential for the accurate biosynthesis and full activity of the mature products. Establishment of an effective peptide profile is dependent on not only the presence of peptide precursor, but also the presence and the enzymatic specificities of cleavage enzymes. We have, therefore, characterized the spatial and temporal patterns of six subtilisin-like serine endoproteases known to be involved in proprotein processing, including furin, PC1, PC2, PC4, PC5, and PACE4, in rat prenatal development and related the results to the expression patterns of several peptide precursors. We have observed largely distinct and sometimes complementary expression patterns of individual PCs in various embryonic structures, suggesting PCs may be functionally distinct in processing different sets of proprotein substrates in development. From these studies, numerous tentative enzyme-substrate relationships in various embryonic structures have been proposed and should encourage more studies to test the in vitro cleavage potentialities of individual PCs toward these precursors. In the future, knowledge gained from these studies, when combined with insights gained from in vivo perturbation and genetic ablation studies, should lead to final comprehensive understanding of specific precursors cleaved by specific enzymes at specific cleavage sites in known spatial and temporal expression patterns during development.
Zheng
M
M
Department of Neuroscience and Cell Biology, UMDNJ-Robert Wood Johnson Medical School, Piscataway 08854, USA.
Pintar
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JE
D000818:Animals; D005314:Embryonic and Fetal Development / Q000235:genetics / Q000502:physiology*; D005260:Female; D045683:Furin; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D017403:In Situ Hybridization; D015394:Molecular Structure; D011247:Pregnancy; D011499:Protein Processing, Post-Translational; D018075:RNA, Complementary / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013381:Subtilisins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D014018:Tissue Distribution
D018075:RNA, Complementary; D013381:Subtilisins; D045683:Furin