Cleavage of chromogranin A N-terminal domain by plasmin provides a new mechanism for regulating cell adhesion

Barbara Colombo, Renato Longhi, Chiara Marinzi, Fulvio Magni, Angela Cattaneo, Seung Hyun Yoo, Flavio Curnis, Angelo Corti

Research output: Contribution to journalArticlepeer-review


It has been proposed that chromogranin A (CgA), a protein secreted by many normal and neoplastic neuroendocrine cells, can play a role as a positive or a negative modulator of cell adhesion. The mechanisms that regulate these extracellular functions of CgA are unknown. We show here that plasmin can regulate the anti/pro-adhesive activity of CgA by proteolytic cleavage of the N-terminal domain. Limited proteolytic processing decreased its anti-adhesive activity and induced pro-adhesive effects in fibronectin or serum-dependent fibroblast adhesion assays. Cleavage of Lys77-Lys78 dibasic site in CgA1-115 was relatively rapid and associated with an increase of pro-adhesive effect. In contrast, antibodies against the region 53-90 enhanced the anti-adhesive activity of CgA and CgA1-115. Structure-activity relationship studies showed that the conserved region 47-64 (RILSILRHQNLLKELQDL) is critical for both pro- and anti-adhesive activity. These findings suggest that CgA might work on one hand as a negative modulator of cell adhesion and on the other hand as a precursor of positive modulators, the latter requiring proteolytic processing for activation. Given the importance of plasminogen activation in tissue invasion and remodeling, the interplay between CgA and plasmin could provide a novel mechanism for regulating fibroblast adhesion and function in neuroendocrine tumors.

Original languageEnglish
Pages (from-to)45911-45919
Number of pages9
JournalJournal of Biological Chemistry
Issue number48
Publication statusPublished - Nov 29 2002

ASJC Scopus subject areas

  • Biochemistry


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