Comparative aspects of intracellular proteolytic processing of peptide hormone precursors: studies of proopiomelanocortin processing.
In this review, the mechanisms underlying the intracellular processing of peptide hormone precursors, with a focus on proopiomelanocortin (POMC), were discussed on the basis of recent information. POMC as well as other prohormones is processed to active peptides through proteolytic cleavage by prohormone convertases PC1 and/or PC2. However, the cleavage-specificity of PC1 and PC2 in mammals is somewhat different from that in amphibians. From the comparative endocrinological point of view, expression and tissue distribution of PC1 and PC2 were discussed here. In mammals, proteolytic processing of POMC occurs coordinately with the maturation of secretory granules. Studies using immunoelectron microscopy with DAMP (3-[2,4-dinitroanilino]-3'-amino-N-methyldipropylamine) as a pH probe revealed that the acidic pH in the secretory granules, generated by vacular type-H+-ATPase, provides a favorable environment for activating PC1 in AtT-20 cells, a mouse corticotrope tumor cell line. Recent data indicate that the 7B2 protein serves as a chaperone in the regulation of PC2 activation and to control the timing for activating the convertase. Together, secretory granules in endocrine and neuroendocrine cells provide proper sites for biosynthesizing hormones in addition to serving as storage sites and vehicles for the transport of peptide hormones.
Tanaka
Shigeyasu
S
Department of Biology, Faculty of Science, Shizuoka University, Shizuoka, Japan. sbstana@ipc.shizuoka.ac.jp
D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011333:Pro-Opiomelanocortin / Q000378:metabolism*; D045664:Proprotein Convertase 1 / Q000378:metabolism*; D045706:Proprotein Convertase 2 / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D022142:Secretory Vesicles / Q000378:metabolism*
D011333:Pro-Opiomelanocortin; D045664:Proprotein Convertase 1; D045706:Proprotein Convertase 2