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Urokinase-type plasminogen activator and its receptor synergize to promote pathogenic proteolysis

Zhou, Hong-Ming
Nichols, Anthony
Published in EMBO journal. 2000, vol. 19, no. 17, p. 4817-26
Abstract Urokinase-type plasminogen activator (uPA) is a potent catalyst of extracellular proteolysis, which also binds to a high-affinity plasma membrane receptor (uPAR). Binding of uPA may influence pericellular proteolysis and/or activate intracellular signal transduction. Transgenic mice overexpressing either uPA or uPAR in basal epidermis and hair follicles had no detectable cutaneous alterations. In contrast, bi-transgenic mice overexpressing both uPA and uPAR, obtained by crossing the two transgenic lines, developed extensive alopecia induced by involution of hair follicles, epidermal thickening and sub-epidermal blisters. The phenotype was due to uPA catalytic activity since combined overexpression of uPAR and uPAR-binding but catalytically inactive uPA in the same tissue was not detrimental in another bi-transgenic line. It was accompanied by increased plasmin-generating capacity, up-regulation and activation of matrix metalloproteinases type-2 and -9, and cleavage of uPAR. Thus, combined overexpression of uPA and uPAR acts in synergy to promote pathogenic extracellular proteolysis.
Keywords AnimalsBase SequenceCatalysisCells, CulturedDNA PrimersHydrolysisKeratinocytes/cytology/enzymology/metabolismMiceMice, TransgenicPhenotypeReceptors, Cell Surface/genetics/metabolismReceptors, Urokinase Plasminogen ActivatorTransgenesUrokinase-Type Plasminogen Activator/genetics/metabolism
PMID: 10970872
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ZHOU, Hong-Ming et al. Urokinase-type plasminogen activator and its receptor synergize to promote pathogenic proteolysis. In: EMBO journal, 2000, vol. 19, n° 17, p. 4817-26. doi: 10.1093/emboj/19.17.4817 https://archive-ouverte.unige.ch/unige:3897

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Deposited on : 2009-10-23

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