title: Identification of a thrombin cleavage site and a short form of ADAMTS-18.
abstract: We previously reported that C-terminal fragment of ADAMTS-18 induces platelet fragmentation through ROS release. We have shown that thrombin cleaves ADAMTS-18 and that a short form of ADAMTS-18 in in vitro translational assay. However, the exact thrombin cleavage site and whether a short form ADAMTS-18 presents in vivo are not clear. In this study, we first identified that the thrombin cleavage site is between Arg775 and Ser776 by thrombin cleavage of ADAMTS-18 peptide following mass spectrum assay. We then showed that a short form ADAMTS-18 presents in brain, kidney, lung, and testicle from C57BL/6 mouse embryo. Since alternative form of ADAMTS-18 could be a mechanism to regulate its activity, we then investigated the mechanism involves in the generation of ADAMTS-18 short form. However, neither protease inhibitors nor mutations in catalytic domain of ADAMTS-18 have any significant effect on the generation of ADAMTS-18 short form. Thus, our data demonstrate a thrombin cleavage site and confirm a short form of ADAMTS-18 presents in vivo.
authors.affiliation: Department of Medicine, NYU Cancer Institute, New York University School of Medicine, 550 First Avenue, New York, NY 10016, United States.
authors.forename: Jianhui
authors.initials: J
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Zanhua
authors.initials: Z
authors.lastname: Yi
authors.forename: Shiyang
authors.initials: S
authors.lastname: Wang
authors.forename: Zongdong
authors.initials: Z
authors.lastname: Li
mesh_terms: D051722:ADAM Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics; D000071096:ADAMTS Proteins; D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000737:chemistry / Q000235:genetics; D020134:Catalytic Domain; D003062:Codon / Q000235:genetics; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D012694:Serine / Q000737:chemistry / Q000235:genetics; D013917:Thrombin / Q000737:chemistry*; D014018:Tissue Distribution
chemical_list: D003062:Codon; D015853:Cysteine Proteinase Inhibitors; D012694:Serine; D001120:Arginine; D013917:Thrombin; D051722:ADAM Proteins; D000071096:ADAMTS Proteins; C570607:ADAMTS18 protein, mouse