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Role of extracellular signal‐regulated protein kinase cascade in macrophage killing of Candida albicans
Author(s) -
IbataOmbetta Stella,
Jouault Thierry,
Trinel PierreAndré,
Poulain Daniel
Publication year - 2001
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.70.1.149
Subject(s) - biology , candida albicans , kinase , mapk/erk pathway , mitogen activated protein kinase kinase , protein kinase a , ribosomal s6 kinase , phosphatase , map kinase kinase kinase , microbiology and biotechnology , ask1 , c raf , mitogen activated protein kinase , map2k7 , corpus albicans , phosphorylation , cyclin dependent kinase 2 , biochemistry , p70 s6 kinase 1 , protein kinase b
The pathogenic yeast Candida albicans and its derivedmolecules stimulate a wide range of macrophage secretory functions andmay adapt to escape being killed by this phagocyte. In this study,phagocytosis of C. albicans and of the nonpathogenic yeast Saccharomyces cerevisiae was shown to be associated withphosphorylation of the mitogen‐activated protein kinase(MAPK)/extracellularly regulated kinase (ERK) pathway in the absence ofsignificant activation of either p38MAPK or stress‐activated proteinkinase/c‐Jun N‐terminal kinase. However, although 80% of endocytosed C. albicans survived after 1 h, 80% of S.cerevisiae cells were killed. Considerable quantitativedifferences were observed between the two species in the sequentialphosphorylation of MAPK/ERK kinase (MEK), extracellularly regulatedkinase‐1, and 90‐kDa‐ribosomal S6 kinases. A lower level of activationof the pathway by C. albicans was associated with aspecies‐specific overexpression of the MEK phosphatase MAPK phosphatase(MKP)‐1. Killing of both C. albicans and S.cerevisiae could be reduced using PD98059, which mimics MKP‐1 andinhibits MEK phosphorylation, suggesting that specific MKP‐1 activationby C. albicans could contribute to its ability to escapethe yeast lytic potential of macrophages.