Versican V1 proteolysis in human aorta in vivo occurs at the Glu441-Ala442 bond, a site that is cleaved by recombinant ADAMTS-1 and ADAMTS-4.
Mature human aorta contains a 70-kDa versican fragment, which reacts with a neoepitope antiserum to the C-terminal peptide sequence DPEAAE. This protein therefore appears to represent the G1 domain of versican V1 (G1-DPEAAE(441)), which has been generated in vivo by proteolytic cleavage at the Glu(441)-Ala(442) bond, within the sequence DPEAAE(441)-A(442)RRGQ. Because the equivalent aggrecan product (G1-NITEGE(341)) and brevican product (G1-EAVESE(395)) are generated by ADAMTS-mediated cleavage of the respective proteoglycans, we tested the capacity of recombinant ADAMTS-1 and ADAMTS-4 to cleave versican at Glu(441)-Ala(442). Both enzymes cleaved a recombinant versican substrate and native human versican at the Glu(441)-Ala(442) bond and the mature form of ADAMTS-4 was detected by Western analysis of extracts of aortic intima. We conclude that versican V1 proteolysis in vivo can be catalyzed by one or more members of the ADAMTS family of metalloproteinases.
Shriners Hospital for Children, Tampa, Florida 33612, USA. jsandy@shctampa.usf.edu
J D
JD
Sandy
J
J
Westling
R D
RD
Kenagy
M L
ML
Iruela-Arispe
C
C
Verscharen
J C
JC
Rodriguez-Mazaneque
D R
DR
Zimmermann
J M
JM
Lemire
J W
JW
Fischer
T N
TN
Wight
A W
AW
Clowes
D051722:ADAM Proteins; D000071097:ADAMTS1 Protein; D000071121:ADAMTS4 Protein; D000409:Alanine; D001012:Aorta, Abdominal / Q000378:metabolism*; D002478:Cells, Cultured; D011508:Chondroitin Sulfate Proteoglycans / Q000737:chemistry* / Q000378:metabolism*; D019483:Disintegrins / Q000378:metabolism*; D018698:Glutamic Acid; D006801:Humans; D037181:Lectins, C-Type; D008666:Metalloendopeptidases / Q000378:metabolism*; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011348:Procollagen N-Endopeptidase; D011509:Proteoglycans / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013379:Substrate Specificity; D017539:Tunica Intima / Q000378:metabolism; D053675:Versicans
D011508:Chondroitin Sulfate Proteoglycans; D019483:Disintegrins; D037181:Lectins, C-Type; D010446:Peptide Fragments; D011509:Proteoglycans; D011994:Recombinant Proteins; C508322:VCAN protein, human; D053675:Versicans; D018698:Glutamic Acid; D051722:ADAM Proteins; D000071097:ADAMTS1 Protein; C103859:ADAMTS1 protein, human; D008666:Metalloendopeptidases; D011348:Procollagen N-Endopeptidase; D000071121:ADAMTS4 Protein; C000603918:ADAMTS4 protein, human; D000409:Alanine