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dc.contributor.authorOkada, Kazushi
dc.contributor.authorMoon, Hee-Jung
dc.contributor.authorFinney, Joel
dc.contributor.authorMeier, Alex
dc.contributor.authorMure, Minae
dc.date.accessioned2019-11-08T20:42:27Z
dc.date.available2019-11-08T20:42:27Z
dc.date.issued2018-11-30
dc.identifier.citationOkada, K., Moon, H. J., Finney, J., Meier, A., & Mure, M. (2018). Extracellular Processing of Lysyl Oxidase-like 2 and Its Effect on Amine Oxidase Activity. Biochemistry, 57(51), 6973–6983. doi:10.1021/acs.biochem.8b01008en_US
dc.identifier.urihttp://hdl.handle.net/1808/29753
dc.descriptionThis document is the Accepted Manuscript version of a Published Work that appeared in final form in Biochemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://doi.org/10.1021/acs.biochem.8b01008.en_US
dc.description.abstractOverexpression of lysyl oxidase-like 2 (LOXL2) is associated with several hepatic and vascular fibrotic diseases and tumor progression in some aggressive cancers. Secreted LOXL2 promotes extracellular matrix cross-linking by catalyzing the oxidative deamination of peptidyl lysine. A great deal remains to be learned about the post-translational modifications of LOXL2, including whether such modifications modulate enzymatic and disease-promoting activities; such knowledge would inform the development of potential therapies. We discovered that upon secretion in cell culture, LOXL2 undergoes proteolytic processing of the first two of four scavenger receptor cysteine-rich domains at the N-terminus. A similar pattern of processing was also evident in tissue extracts from an invasive ductal carcinoma patient. Processing occurred at 314Arg-315Phe-316Arg-317Lys↓-318Ala-, implicating proprotein convertases. siRNA-mediated knockdown of proprotein convertases (furin, PACE4, and PC5/6), as well as incubation with their recombinant forms, showed that PACE4 is the major protease that acts on extracellular LOXL2. Unlike LOX, which requires cleavage of its propeptide for catalytic activation, cleavage of LOXL2 was not essential for tropoelastin oxidation or for cross-linking of collagen type IV in vitro. However, in the latter case, processing enhanced the extent of collagen cross-linking ∼2-fold at ≤10 nM LOXL2. These results demonstrate an important difference in the regulatory mechanisms for LOX and LOXL2 catalytic activity. Moreover, they pave the way for further studies of potential differential functions of LOXL2 isoforms in fibrosis and tumor progression.en_US
dc.publisherAmerican Chemical Societyen_US
dc.rightsCopyright © 2018 American Chemical Societyen_US
dc.titleExtracellular Processing of Lysyl Oxidase-like 2 and Its Effect on Amine Oxidase Activityen_US
dc.typeArticleen_US
kusw.kuauthorOkada, Kazushi
kusw.kuauthorMoon, Hee-Jung
kusw.kuauthorFinney, Joel
kusw.kuauthorMeier, Alex
kusw.kuauthorMure, Minae
kusw.kudepartmentChemistryen_US
dc.identifier.doi10.1021/acs.biochem.8b01008en_US
dc.identifier.orcidhttps://orcid.org/0000-0001-6768-7810en_US
kusw.oaversionScholarly/refereed, author accepted manuscripten_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US
dc.identifier.pmidPMC6548334en_US
dc.rights.accessrightsOpenAccessen_US


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