Furin is a chemokine-modifying enzyme: in vitro and in vivo processing of CXCL10 generates a C-terminally truncated chemokine retaining full activity

P Hensbergen, D. Verzijl, C.I. Balog, R. Dijkman, R van der Schors, E.M.H. van der Raaij-Helmer, M.. van der Plas, R. Leurs, A.M. Deelder, M.J. Smit, C.P. Tensen

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Abstract

Chemokines comprise a class of structurally related proteins that are involved in many aspects of leukocyte migration under basal and inflammatory conditions. In addition to the large number of genes, limited processing of these proteins by a variety of enzymes enhances the complexity of the total spectrum of chemokine variants. We have recently shown that the native chemokine CXCL10 is processed at the C terminus, thereby shedding the last four amino acids. The present study was performed to elucidate the mechanism in vivo and in vitro and to study the biological activity of this novel isoform of CXCL10. Using a combination of protein purification and mass spectrometric techniques, we show that the production of C-terminally truncated CXCL10 by primary keratinocytes is inhibited in vivo by a specific inhibitor of pro-protein convertases (e.g. furin) but not by inhibition of matrix metalloproteinases. Moreover, CXCL10 is processed by furin in vitro, which is abrogated by a mutation in the furin recognition site. Using GTRγS binding, Ca
Original languageEnglish
Pages (from-to)13402-11
JournalJournal of Biological Chemistry
Volume279
Issue number14
DOIs
Publication statusPublished - 2004

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