The neuroendocrine polypeptide 7B2 is an endogenous inhibitor of prohormone convertase PC2.
The subtilisin-like prohormone convertase PC2 and the polypeptide 7B2 (an intracellularly cleaved protein of unknown function) are both selectively present in the regulated secretory pathway of neurons and endocrine cells. Here we demonstrate that intact recombinant 7B2 is a potent inhibitor of PC2 and prevents proPC2 cleavage in vitro, whereas the 7B2 cleavage product is virtually inactive. The PC2-related proteinase PC1/PC3 is not inhibited by 7B2. Furthermore, the carboxyl-terminal half of the 7B2 protein sequence is distantly related to the so-called potato inhibitor I family (which includes subtilisin inhibitors). Our findings indicate that 7B2 is a physiological inhibitor of PC2 and may provide alternative avenues for the manipulation of peptide hormone levels.
Department of Animal Physiology, University of Nijmegen, The Netherlands.
G J
GJ
Martens
J A
JA
Braks
D W
DW
Eib
Y
Y
Zhou
I
I
Lindberg
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D004926:Escherichia coli; D006801:Humans; D007700:Kinetics; D007865:Leeches; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D051859:Neuroendocrine Secretory Protein 7B2; D009490:Neurosecretory Systems / Q000201:enzymology / Q000502:physiology; D010907:Pituitary Hormones / Q000096:biosynthesis / Q000737:chemistry / Q000494:pharmacology*; D010944:Plants; D045706:Proprotein Convertase 2; D011480:Protease Inhibitors / Q000737:chemistry; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D015183:Restriction Mapping; D017386:Sequence Homology, Amino Acid; D013381:Subtilisins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000302:isolation & purification
D009419:Nerve Tissue Proteins; D051859:Neuroendocrine Secretory Protein 7B2; D010907:Pituitary Hormones; D011480:Protease Inhibitors; D011994:Recombinant Proteins; C497678:SCG5 protein, human; D013381:Subtilisins; D045706:Proprotein Convertase 2