Progastrin processing differs in 7B2 and PC2 knockout animals: a role for 7B2 independent of action on PC2.
Cellular synthesis of neuroendocrine peptides requires prohormone convertases (PCs). In order to determine the role of PC2 for gastrin synthesis, we examined antral extracts from mice lacking PC2 or its chaperone, 7B2. The overall concentrations of precursors and alpha-amidated gastrins were similar in all mice. Chromatography, however, revealed that while the K(53)-K(54) site was almost fully cleaved in controls and half cleaved in PC2 null mice, only 23% was cleaved in 7B2 null mice. The results show that PC2 and 7B2 both are required for synthesis of the main form of gastrin (gastrin-17), and that 7B2 exhibits effects beyond PC2-mediated cleavages.
Rehfeld
Jens F
JF
Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. rehfeld@rh.dk
Lindberg
Iris
I
Friis-Hansen
Lennart
L
D000818:Animals; D002850:Chromatography, Gel / Q000379:methods; D005260:Female; D005755:Gastrins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018832:Molecular Chaperones / Q000235:genetics / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D051859:Neuroendocrine Secretory Protein 7B2; D009490:Neurosecretory Systems / Q000378:metabolism*; D010907:Pituitary Hormones / Q000235:genetics / Q000502:physiology*; D045706:Proprotein Convertase 2; D011498:Protein Precursors / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D013381:Subtilisins / Q000235:genetics / Q000502:physiology*
D005755:Gastrins; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; D051859:Neuroendocrine Secretory Protein 7B2; D010907:Pituitary Hormones; D011498:Protein Precursors; C083040:gastrin desulfonated; C013706:big gastrin; C013550:gastrin 17; D013381:Subtilisins; D045706:Proprotein Convertase 2