title: Chymotrypsin C is a co-activator of human pancreatic procarboxypeptidases A1 and A2.
abstract: Human digestive carboxypeptidases CPA1, CPA2, and CPB1 are secreted by the pancreas as inactive proenzymes containing a 94-96-amino acid-long propeptide. Activation of procarboxypeptidases is initiated by proteolytic cleavage at the C-terminal end of the propeptide by trypsin. Here, we demonstrate that subsequent cleavage of the propeptide by chymotrypsin C (CTRC) induces a nearly 10-fold increase in the activity of trypsin-activated CPA1 and CPA2, whereas CPB1 activity is unaffected. Other human pancreatic proteases such as chymotrypsin B1, chymotrypsin B2, chymotrypsin-like enzyme-1, elastase 2A, elastase 3A, or elastase 3B are inactive or markedly less effective at promoting procarboxypeptidase activation. On the basis of these observations, we propose that CTRC is a physiological co-activator of proCPA1 and proCPA2. Furthermore, the results confirm and extend the notion that CTRC is a key regulator of digestive zymogen activation.
authors.affiliation: Department of Molecular and Cell Biology, Boston University Henry M. Goldman School of Dental Medicine, Boston, Massachusetts 02118, USA.
authors.forename: Richárd
authors.initials: R
authors.lastname: Szmola
authors.forename: Melinda
authors.initials: M
authors.lastname: Bence
authors.forename: Andrea
authors.initials: A
authors.lastname: Carpentieri
authors.forename: András
authors.initials: A
authors.lastname: Szabó
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Costello
authors.forename: John
authors.initials: J
authors.lastname: Samuelson
authors.forename: Miklós
authors.initials: M
authors.lastname: Sahin-Tóth
mesh_terms: D043422:Carboxypeptidases A / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002918:Chymotrypsin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D020536:Enzyme Activators / Q000737:chemistry* / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D010179:Pancreas / Q000201:enzymology*; D014357:Trypsin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D020536:Enzyme Activators; D043422:Carboxypeptidases A; D002918:Chymotrypsin; C117569:chymotrypsin C; D014357:Trypsin