Titre
MARCKS-related protein (MRP) is a substrate for the Leishmania major surface protease leishmanolysin (gp63).
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
PĂ©riodique
Auteur(s)
Corradin, S.
Auteure/Auteur
Ransijn, A.
Auteure/Auteur
Corradin, G.
Auteure/Auteur
Roggero, M.A.
Auteure/Auteur
Schmitz, A.A.
Auteure/Auteur
Schneider, P.
Auteure/Auteur
Mauël, J.
Auteure/Auteur
Vergères, G.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
0021-9258
Statut Ă©ditorial
Publié
Date de publication
1999
Volume
274
Numéro
36
Première page
25411
Dernière page/numéro d’article
25418
Langue
anglais
Résumé
Myristoylated alanine-rich C kinase substrate (MARCKS) and MARCKS-related protein (MRP; MacMARCKS) are protein kinase C substrates in diverse cell types. Activation of murine macrophages by cytokines increases MRP expression, but infection with Leishmania promastigotes during activation results in MRP depletion. We therefore examined the effect of Leishmania major LV39 on recombinant MRP. Both live promastigotes and a soluble fraction of LV39 lysates degraded MRP to yield lower molecular weight fragments. Degradation was independent of MRP myristoylation and was inhibited by protein kinase C-dependent phosphorylation of MRP. MRP was similarly degraded by purified leishmanolysin (gp63), a Leishmania surface metalloprotease. Degradation was evident at low enzyme/substrate ratios, over a broad pH range, and was inhibited by 1,10-phenanthroline and by a hydroxamate dipeptide inhibitor of leishmanolysin. Using mass spectrometric analysis, cleavage was shown to occur within the effector domain of MRP between Ser(92) and Phe(93), in accordance with the substrate specificity of leishmanolysin. Moreover, an MRP construct in which the effector domain had been deleted was resistant to cleavage. Thus, Leishmania infection may result in leishmanolysin-dependent hydrolysis of MRP, a major protein kinase C substrate in macrophages.
PID Serval
serval:BIB_09CCF8818B94
PMID
Open Access
Oui
Date de création
2008-01-24T13:55:30.510Z
Date de création dans IRIS
2025-05-20T15:21:25Z
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Nom
038. Corradin et al.pdf
Version du manuscrit
preprint
Taille
406.18 KB
Format
Adobe PDF
PID Serval
serval:BIB_09CCF8818B94.P001
URN
urn:nbn:ch:serval-BIB_09CCF8818B947
Somme de contrĂ´le
(MD5):92939d289d68af906e27da172c300c5b