Stromal cell-derived factors 1alpha and 1beta, inflammatory protein-10 and interferon-inducible T cell chemo-attractant are novel substrates of dipeptidyl peptidase 8.
N-terminal truncation of chemokines by proteases including dipeptidyl peptidase (DP) IV significantly alters their biological activity; generally ablating cognate G-protein coupled receptor engagement and often generating potent receptor antagonists. DP8 is a recently recognised member of the prolyl oligopeptidase gene family that includes DPIV. Since DPIV is known to process chemokines we surveyed 27 chemokines for cleavage by DP8. We report DP8 cleavage of the N-terminal two residues of IP10 (CXCL10), ITAC (CXCL11) and SDF-1 (CXCL12). This has implications for DP8 substrate specificity. Chemokine cleavage and inactivation may occur in vivo upon cell lysis and release of DP8 or in the inactivation of internalized chemokine/receptor complexes.
Ajami
Katerina
K
Centenary Institute, Faculty of Medicine, University of Sydney, Newtown, Sydney, NSW, Australia.
Pitman
Melissa R
MR
Wilson
Claire H
CH
Park
Joohong
J
Menz
R Ian
RI
Starr
Amanda E
AE
Cox
Jennifer H
JH
Abbott
Catherine A
CA
Overall
Christopher M
CM
Gorrell
Mark D
MD
D054357:Chemokine CXCL10 / Q000737:chemistry / Q000378:metabolism*; D054371:Chemokine CXCL11 / Q000737:chemistry / Q000378:metabolism*; D054377:Chemokine CXCL12 / Q000737:chemistry / Q000378:metabolism*; D004150:Dipeptidases / Q000302:isolation & purification / Q000378:metabolism*; D018819:Dipeptidyl Peptidase 4 / Q000302:isolation & purification / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D008970:Molecular Weight; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D012995:Solubility; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013379:Substrate Specificity
D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054377:Chemokine CXCL12; D011994:Recombinant Proteins; D004150:Dipeptidases; C042807:DPP4 protein, human; C487997:DPP8 protein, human; D018819:Dipeptidyl Peptidase 4