Characterization of a serine protease that cleaves pro-gamma-melanotropin at the adrenal to stimulate growth.
The adrenal gland requires stimuli from peptides derived from the ACTH precursor, pro-opiomelanocortin (POMC), to maintain its tonic state. Studies have proposed that a specific postsecretional cleavage of the nonmitogenic N-terminal 16 kDa fragment, also known as pro-gamma-melanotropin (pro-gamma-MSH), is required, releasing shorter fragments that promote adrenal growth. Here, we provide evidence for this hypothesis by the cloning and characterization of a serine protease that is upregulated during growth of the adrenal cortex. It is expressed exclusively in the outer adrenal cortex, the site of cell proliferation, and in the Y1 adrenal cell line. We also show that it is required for growth of Y1 cells, remains bound to the cell surface, and cleaves its substrate, pro-gamma-MSH, at a specific bond.
Bicknell
A B
AB
School of Animal and Microbial Sciences, The University of Reading, Whiteknights, PO BOX 228, Reading, Berkshire, RG6 6AJ, United Kingdom. a.b.bicknell@rdg.ac.uk
Lomthaisong
K
K
Woods
R J
RJ
Hutchinson
E G
EG
Bennett
H P
HP
Gladwell
R T
RT
Lowry
P J
PJ
D000302:Adrenal Cortex / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D000311:Adrenal Glands / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D000315:Adrenalectomy; D000595:Amino Acid Sequence; D000818:Animals; D007611:Aprotinin / Q000494:pharmacology; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D017403:In Situ Hybridization; D008297:Male; D009074:Melanocyte-Stimulating Hormones / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000378:metabolism*; D051381:Rats; D016415:Sequence Alignment; D012697:Serine Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology
D010446:Peptide Fragments; D015842:Serine Proteinase Inhibitors; D011333:Pro-Opiomelanocortin; D009074:Melanocyte-Stimulating Hormones; D007611:Aprotinin; D012697:Serine Endopeptidases; C431509:adrenal secretory protease