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[PMID]: | 28003343 |
[Au] Autor: | Bedau T; Peters F; Prox J; Arnold P; Schmidt F; Finkernagel M; Köllmann S; Wichert R; Otte A; Ohler A; Stirnberg M; Lucius R; Koudelka T; Tholey A; Biasin V; Pietrzik CU; Kwapiszewska G; Becker-Pauly C |
[Ad] Endereço: | Unit for Degradomics of the Protease Web, Institute of Biochemistry, University of Kiel, Kiel, Germany. |
[Ti] Título: | Ectodomain shedding of CD99 within highly conserved regions is mediated by the metalloprotease meprin ß and promotes transendothelial cell migration. |
[So] Source: | FASEB J;31(3):1226-1237, 2017 Mar. | [Is] ISSN: | 1530-6860 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | The adhesion molecule CD99 is essential for the transendothelial migration of leukocytes. In this study, we used biochemical and cellular assays to show that CD99 undergoes ectodomain shedding by the metalloprotease meprin ß and subsequent intramembrane proteolysis by γ-secretase. The cleavage site in CD99 was identified by mass spectrometry within an acidic region highly conserved through different vertebrate species. This finding fits perfectly to the unique cleavage specificity of meprin ß with a strong preference for aspartate residues and suggests coevolution of protease and substrate. We hypothesized that limited CD99 cleavage by meprin ß would alter cellular transendothelial migration (TEM) behavior in tissue remodeling processes, such as inflammation and cancer. Indeed, meprin ß induced cell migration of Lewis lung carcinoma cells in an TEM assay. Accordingly, deficiency of meprin ß in mice resulted in significantly increased CD99 protein levels in the lung. Therefore, meprin ß could serve as a therapeutic target, given that in a proof-of-concept approach we showed accumulation of CD99 protein in lungs of meprin ß inhibitor-treated mice.-Bedau, T., Peters, F., Prox, J., Arnold, P., Schmidt, F., Finkernagel, M., Köllmann, S., Wichert, R., Otte, A., Ohler, A., Stirnberg, M., Lucius, R., Koudelka, T., Tholey, A., Biasin, V., Pietrzik, C. U., Kwapiszewska, G., Becker-Pauly, C. Ectodomain shedding of CD99 within highly conserved regions is mediated by the metalloprotease meprin ß and promotes transendothelial cell migration. |
[Mh] Termos MeSH primário: |
Antígeno 12E7/metabolismo Sequência Conservada Metaloendopeptidases/metabolismo Proteólise Migração Transendotelial e Transepitelial
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[Mh] Termos MeSH secundário: |
Antígeno 12E7/química Animais Carcinoma Pulmonar de Lewis/metabolismo Células HEK293 Células HeLa Seres Humanos Camundongos Camundongos Endogâmicos C57BL
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[Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (12E7 Antigen); EC 3.4.24.- (Metalloendopeptidases); EC 3.4.24.18 (meprin A) |
[Em] Mês de entrada: | 1709 |
[Cu] Atualização por classe: | 171116 |
[Lr] Data última revisão:
| 171116 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 161223 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1096/fj.201601113R |
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