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The Subtilisin/Kexin Family of Precursor Convertases: Emphasis on PC1, PC2/7B2, POMC and the Novel Enzyme SKI‐1
Author(s) -
SEIDAH NABIL G.,
BENJANNET SUZANNE,
HAMELIN JOSÉE,
MAMARBACHI AIDA M.,
BASAK AJOY,
MARCINKIEWICZ JADWIGA,
MBIKAY MAJAMBU,
CHRÉTIEN MICHEL,
MARCINKIEWICZ MIECZYSLAW
Publication year - 1999
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1999.tb08665.x
Subject(s) - proopiomelanocortin , zymogen , enzyme , biochemistry , biology , prohormone convertase , chemistry , endocrinology , medicine , hypothalamus , hormone , prohormone
Proopiomelanocortin (POMC) is a precursor to various, bioactive peptides including ACTH, βLPH, αMSH, and βendorphin (βEND). Processing of POMC at dibasic residues is tissue‐specific and is performed by either PC1 alone (resulting in ACTH and βLPH, anterior pituitary corticotrophes) or by a combination of PC1 and PC2 (yielding αMSH and βEND, pituitary neurointermediate lobe and hypothalamus). The PC2‐specific binding protein 7B2 is intimately involved in the zymogen activation of proPC2 into PC2. Structure‐function studies of these enzymes demonstrated the presence of N‐ and C‐terminal domains, as well as specific amino acids within the catalytic segment that influence the degree of activity of each enzyme and the interaction of PC2 with 7B2. The tissue distribution, plasticity of expression, and the multiple precursors that are differentially cleaved by PC1 and/or PC2, predict a wide array of combinatorial activities of these convertases within the endocrine and neuroendocrine system. The phenotypic consequences of the absence of genetic expression of either PC1 or PC2 are now explored using knockout mice and in human patients suffering from obesity and diabetes.