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The protease MT1‐MMP drives a combinatorial proteolytic program in activated endothelial cells
Author(s) -
Koziol Agnieszka,
Gonzalo Pilar,
Mota Alba,
Pollán Ángela,
Lorenzo Cristina,
Colomé Nuria,
Montaner David,
Dopazo Joaquín,
Arribas Joaquín,
Canals Francesc,
Arroyo Alicia G.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.12-205906
Subject(s) - proteolysis , protease , angiogenesis , microbiology and biotechnology , matrix metalloproteinase , proteases , context (archaeology) , chemistry , proteolytic enzymes , biology , biochemistry , cancer research , enzyme , paleontology
The mechanism by which proteolytic events translate into biological responses is not well understood. To explore the link of pericellular proteolysis to events relevant to capillary sprouting within the inflammatory context, we aimed at the identification of the collection of substrates of the protease MT1‐MMP in endothelial tip cells induced by inflammatory stimuli. We applied quantitative proteomics to endothelial cells (ECs) derived from wild‐type and MT1‐MMP‐null mice to identify the substrate repertoire of this protease in TNF‐α‐activated ECs. Bioinformatics analysis revealed a combinatorial MT1‐MMP proteolytic program, in which combined rather than single substrate processing would determine biological decisions by activated ECs, including chemotaxis, cell motility and adhesion, and vasculature development. MT1‐MMP‐deficient ECs inefficiently processed several of these substrates (TSP1, CYR61, NID1, and SEM3C), validating the model. This novel concept of MT1‐MMP‐driven combinatorial proteolysis in angiogenesis might be extendable to proteolytic actions in other cellular contexts.—Koziol, A., Gonzalo, P., Mota, A., Pollán, Á., Lorenzo, C., Colomé, N., Montaner, D., Dopazo, J., Arribas, J., Canals, F., Arroyo, A. G. The protease MT1‐MMP drives a combinatorial proteolytic program in activated endothelial cells. FASEB J. 26, 4481–4494 (2012). www.fasebj.org