PC2 and 7B2 null mice demonstrate that PC2 is essential for normal pro-CCK processing.
Analysis of CCK content in extracts of whole forebrain from PC2 and 7B2 null mouse brain showed a significant decrease relative to wild-type brains. More detailed analysis revealed that CCK 8 amide levels in cerebral cortex and forebrain regions were more decreased than in hypothalamus. CCK 8 content in PC2 null mouse intestines was identical to control. Null mutant brains contained less CCK 8 than wild type and no other forms were seen when analyzed by gel filtration chromatography. No brain area examined was completely devoid of CCK, suggesting that other enzymes can partially compensate for the loss of PC2. This is the first demonstration that any endoprotease is important for CCK processing but also suggest the presence of a redundant system to ensure production of active CCK in the brain.
Vishnuvardhan
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D
Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Avenue, Boston, Massachusetts 02111, USA.
Connolly
K
K
Cain
B
B
Beinfeld
M C
MC
D000818:Animals; D002540:Cerebral Cortex / Q000201:enzymology / Q000378:metabolism; D002766:Cholecystokinin / Q000378:metabolism*; D002850:Chromatography, Gel; D005260:Female; D017353:Gene Deletion; D007031:Hypothalamus / Q000201:enzymology / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000201:enzymology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051859:Neuroendocrine Secretory Protein 7B2; D010446:Peptide Fragments / Q000378:metabolism; D010907:Pituitary Hormones / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D045706:Proprotein Convertase 2; D016548:Prosencephalon / Q000201:enzymology / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D011863:Radioimmunoassay; D013381:Subtilisins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D009419:Nerve Tissue Proteins; D051859:Neuroendocrine Secretory Protein 7B2; D010446:Peptide Fragments; D010907:Pituitary Hormones; D011498:Protein Precursors; C410885:cholecystokinin 8; C060249:procholecystokinin; D002766:Cholecystokinin; D013381:Subtilisins; D045706:Proprotein Convertase 2