| First Author | Wichert R | Year | 2019 |
| Journal | FASEB J | Volume | 33 |
| Issue | 11 | Pages | 11925-11940 |
| PubMed ID | 31381863 | Mgi Jnum | J:298593 |
| Mgi Id | MGI:6457671 | Doi | 10.1096/fj.201801371R |
| Citation | Wichert R, et al. (2019) Meprin beta induces activities of A disintegrin and metalloproteinases 9, 10, and 17 by specific prodomain cleavage. FASEB J 33(11):11925-11940 |
| abstractText | Meprin beta is a membrane-bound metalloprotease involved in extracellular matrix assembly and inflammatory processes in health and disease. A disintegrin and metalloproteinase (ADAM)10 and ADAM17 are physiologic relevant sheddases of inactive promeprin beta, which influences its substrate repertoire and subsequent biologic functions. Proteomic analysis also revealed several ADAMs as putative meprin beta substrates. Here, we demonstrate specific N-terminal processing of ADAM9, 10, and 17 by meprin beta and identify cleavage sites within their prodomains. Because ADAM prodomains can act as specific inhibitors, we postulate a role for meprin beta in the regulation of ADAM activities. Indeed, prodomain cleavage by meprin beta caused increased ADAM protease activities, as observed by peptide-based cleavage assays and demonstrated by increased ectodomain shedding activity. Direct interaction of meprin beta and ADAM proteases could be shown by immunofluorescence microscopy and immunoprecipitation experiments. As demonstrated by a bacterial activator of meprin beta and additional measurement of TNF-alpha shedding on bone marrow-derived macrophages, meprin beta/ADAM protease interactions likely influence inflammatory conditions. Thus, we identified a novel proteolytic pathway of meprin beta with ADAM proteases to control protease activities at the cell surface as part of the protease web.-Wichert, R., Scharfenberg, F., Colmorgen, C., Koudelka, T., Schwarz, J., Wetzel, S., Potempa, B., Potempa, J., Bartsch, J. W., Sagi, I., Tholey, A., Saftig, P., Rose-John, S., Becker-Pauly, C. Meprin beta induces activities of A disintegrin and metalloproteinases 9, 10, and 17 by specific prodomain cleavage. |
