Chymotrypsin C is a co-activator of human pancreatic procarboxypeptidases A1 and A2

Richárd Szmola, Melinda Bence, Andrea Carpentieri, András Szabó, Catherine E. Costello, John Samuelson, Miklós Sahin-Tóth

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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.

Original languageEnglish
Pages (from-to)1819-1827
Number of pages9
JournalJournal of Biological Chemistry
Issue number3
Publication statusPublished - Jan 21 2011


ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Szmola, R., Bence, M., Carpentieri, A., Szabó, A., Costello, C. E., Samuelson, J., & Sahin-Tóth, M. (2011). Chymotrypsin C is a co-activator of human pancreatic procarboxypeptidases A1 and A2. Journal of Biological Chemistry, 286(3), 1819-1827.