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LmxPK4, a mitogen‐activated protein kinase kinase homologue of Leishmania mexicana with a potential role in parasite differentiation
Author(s) -
Kuhn Daniela,
Wiese Martin
Publication year - 2005
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.2005.04614.x
Subject(s) - biology , leishmania mexicana , amastigote , mutant , protein kinase a , kinase , phenotype , leishmania , leishmania major , microbiology and biotechnology , gene , map kinase kinase kinase , mitogen activated protein kinase , genetics , parasite hosting , world wide web , computer science
Summary Members of the mitogen‐activated protein (MAP) kinase cascade are important for the establishment of a Leishmania mexicana infection and are involved in flagellar length control, although the underlying molecular mechanisms remain to be elucidated. This study reports the cloning and characterization of LmxPK4, a MAP kinase kinase homologue of L. mexicana displaying putative plant‐like regulatory phosphorylation sites . The recombinant protein has autophosphorylating activity and phosphorylates myelin basic protein. An LmxPK4 gene deletion mutant showed a proliferation defect after infection of macrophages and no or delayed lesion development in mice. Irrespective of the onset of lesion development parasites showed an early and homogeneous lesion development in re‐infection experiments. This is indicative for a compensation of the null mutant phenotype. Additionally, this phenotype could be reverted by reintroduction of the wild‐type gene into the deletion background. Mutants expressing loss‐of‐function or N‐terminally truncated versions of LmxPK4 retained the null mutant phenotype. LmxPK4 is stage‐specifically expressed in promastigotes and during differentiation to amastigotes, but is not detectable in amastigotes isolated from the mammalian host. Moreover, its in vitro kinase activity increases with temperature rise up to 40°C. Our results suggest that LmxPK4 is involved in the differentiation process and affects virulence of Leishmania mexicana .