Isolation and functional expression of a mammalian prohormone processing enzyme, murine prohormone convertase 1.
We have combined gene cloning with an assay for prohormone biosynthesis and processing in Xenopus oocytes to identify the genes that encode mammalian prohormone processing enzymes. The coinjection of RNA encoding murine prohormone convertase 1 (mPC1), a mammalian endoprotease, along with proopiomelanocortin RNA into an oocyte results in the appropriate cleavage after paired basic residues in the proopiomelanocortin polyprotein necessary to generate corticotropin. The ability of mPC1 to generate corticotropin, along with the observation that mPC1 is specifically expressed in endocrine and neuronal cells, suggests that the mPC1 gene encodes the endopeptidase responsible for the pathway of proopiomelanocortin cleavage observed in the anterior pituitary.
Korner
J
J
Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032.
Chun
J
J
Harter
D
D
Axel
R
R
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D015870:Gene Expression; D006031:Glycosylation; D051379:Mice; D008969:Molecular Sequence Data; D009865:Oocytes / Q000201:enzymology / Q000502:physiology; D010449:Peptide Mapping; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism; D045664:Proprotein Convertase 1; D043484:Proprotein Convertases; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D051578:Proto-Oncogene Proteins c-fes; D012689:Sequence Homology, Nucleic Acid; D012697:Serine Endopeptidases / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D014982:Xenopus laevis
D011518:Proto-Oncogene Proteins; D011333:Pro-Opiomelanocortin; D011505:Protein-Tyrosine Kinases; C496646:Fes protein, mouse; D051578:Proto-Oncogene Proteins c-fes; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; C473656:Pcsk1 protein, mouse; D045664:Proprotein Convertase 1