Carboxyterminal cleavage of the chemokines MIG and IP-10 by gelatinase B and neutrophil collagenase.
Proteolytic processing is an important regulatory mechanism for chemokines. Matrix metalloproteinases (MMPs), such as gelatinase A/MMP-2 and gelatinase B/MMP-9, are known to process the aminoterminal end of various chemokines, including interleukin-8 (IL-8/CXCL-8) and monocyte chemotactic protein-3 (MCP-3/CXCL-7). In the present study, two proteases, gelatinase B and neutrophil collagenase/MMP-8, are shown for the first time to process the carboxyterminal end of two chemokines, monokine induced by interferon (IFN)-gamma (MIG/CXCL-9) and IFN-inducible protein-10 (IP-10/CXCL-10). Neutrophil collagenase degrades MIG into small fragments and cleaves IP-10 behind positions 71 and 73. Gelatinase B degrades IP-10 and cleaves MIG at three different sites in its extended carboxyterminal region. This results in the formation of MIG(1-94), MIG(1-93), and MIG(1-90). In general, gelatinase B was more efficient than neutrophil collagenase in processing these chemokines. Alignment of the CXC chemokines with the respective cleavage sites by both MMPs identified the ELR motif as a possible determinant for amino terminal cleavage by these MMPs.
Van den Steen
Philippe E
PE
Laboratory of Molecular Immunology, Rega Institute, University of Leuven, Minderbroedersstraat 10, 3000 Leuven, Belgium. philippe.vandensteen@rega.kuleuven.ac.be
Husson
Steven J
SJ
Proost
Paul
P
Van Damme
Jo
J
Opdenakker
Ghislain
G
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001665:Binding Sites; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D018925:Chemokines / Q000378:metabolism; D019743:Chemokines, CXC / Q000494:pharmacology*; D017364:Collagenases / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D007700:Kinetics; D008024:Ligands; D013058:Mass Spectrometry; D020780:Matrix Metalloproteinase 9 / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000201:enzymology* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013997:Time Factors
C080810:CXCL9 protein, human; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D018925:Chemokines; D019743:Chemokines, CXC; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D011994:Recombinant Proteins; D017364:Collagenases; D020780:Matrix Metalloproteinase 9