Molecular cloning demonstrates structural features of homologous bovine prohormone convertases 1 and 2.
PC1 and PC2 (prohormone convertase) represent neuroendocrine members of the mammalian subtilisin-like family of proprotein convertases. The goal of this study was to compare the primary sequence motifs of bovine PC1 and PC2 with those of homologs from other mammalian species to establish the structural basis for PC1 and PC2 activities in bovine that resemble other mammalian homologs. Molecular cloning from bovine adrenal medulla resulted in the isolation of cDNAs for bovine PC1 and PC2 with highly conserved primary sequences with respect to signal sequence, prosegment, catalytic domain, and P domain. Bovine PC1 and PC2 contained the catalytic triad residues Asp, His, Ser, which are identical to the triads in PC1 and PC2 from other mammalian species. Bovine PCl contained Asn as the oxyanion hole residue; in contrast, bovine PC2 contained Asp as the oxyanion hole residue, which is identical to PC2 in other mammalian species. Bovine PC1 and PC2 possessed the P domain that contains the functional RRGDL motif. The cloned cDNAs detected expression of PC1 and PC2 mRNAs in bovine adrenal medulla. These results establish the defined structural domains of bovine PC1 and PC2 that are known to be essential for the activities of these enzymes in various species.
Hwang
S R
SR
Department of Medicine, University of California, San Diego, La Jolla, USA.
Ng
S M
SM
Steineckert
B
B
Seidah
N G
NG
Hook
V Y
VY
D000313:Adrenal Medulla / Q000201:enzymology; D000595:Amino Acid Sequence; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics*; D001483:Base Sequence; D002417:Cattle; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D008969:Molecular Sequence Data; D045706:Proprotein Convertase 2; D043484:Proprotein Convertases; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013381:Subtilisins / Q000235:genetics*
D018076:DNA, Complementary; D043484:Proprotein Convertases; D013381:Subtilisins; D045706:Proprotein Convertase 2; D016282:Aspartic Acid Endopeptidases