Prohormone convertase 2 is necessary for the formation of cholecystokinin-22, but not cholecystokinin-8, in RIN5F and STC-1 cells.
Two endocrine tumor cell lines from pancreas (RIN5F) and intestine (STC-1) express cholecystokinin (CCK) messenger RNA and are able to posttranslationally process pro-CCK to CCK-22 and CCK-8 amide. Both of these forms are also secreted by these cells. Because they make and secrete forms of amidated CCK larger than CCK-8, they represent a model of pro-CCK processing in the gut and allow investigation of possible mechanisms for tissue differences in prohormone processing. Both of these cells express two endoproteases convertase-1 (PC1) also known as PC3 and prohormone convertase-2 (PC2), which may be involved in pro-CCK processing. We have previously shown than inhibition of PC1 expression in these cells using stable expression of antisense messenger RNA caused a significant reduction in cellular content of amidated CCK and caused a selective depletion of CCK-8 with a comparative sparing of CCK-22. We demonstrate here that inhibition of PC2 expression in these cells also caused a large initial decrease in CCK content and produced a selective depletion of CCK-22 and a comparative sparing of CCK-8. These results support both a role for both PC1 and PC2 in pro-CCK processing in these cells and the hypothesis that tissue-specific processing of pro-CCK may be explained by differences in expression or activity of PC1 and PC2.
Yoon
J
J
Department of Pharmacological and Physiological Science, St. Louis University School of Medicine, Missouri 63104, USA.
Beinfeld
M C
MC
D002766:Cholecystokinin / Q000096:biosynthesis* / Q000235:genetics; D015870:Gene Expression; D007414:Intestinal Neoplasms / Q000201:enzymology; D010190:Pancreatic Neoplasms / Q000201:enzymology; D010446:Peptide Fragments / Q000096:biosynthesis* / Q000235:genetics; D045706:Proprotein Convertase 2; D016372:RNA, Antisense / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D012844:Sincalide / Q000096:biosynthesis* / Q000235:genetics; D013381:Subtilisins / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured
D010446:Peptide Fragments; D016372:RNA, Antisense; D012333:RNA, Messenger; D002766:Cholecystokinin; C044926:cholecystokinin 22 C-terminal fragment; D013381:Subtilisins; D045706:Proprotein Convertase 2; D012844:Sincalide