Open AccessParvovirus interference with intracellular signalling: mechanism of PKCη activation in MVM‐infected A9 fibroblasts
Author(s) -
Lachmann Sylvie,
Bär Severine,
Rommelaere Jean,
Nüesch Jürg P. F.
Publication year - 2008
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/j.1462-5822.2007.01082.x
Subject(s) - protein kinase c , phosphorylation , biology , microbiology and biotechnology , kinase , mutant , minute virus of mice , subcellular localization , enzyme activator , parvovirus , biochemistry , virology , virus , parvoviridae , cytoplasm , gene
Summary Autonomous parvoviruses are strongly dependent on the phosphorylation of the major non‐structural protein NS1 by members of the protein kinase C (PKC) family. Besides being accompanied with changes in the overall phosphorylation pattern of NS1 and acquiring new modifications at consensus PKC sites, ongoing minute virus of mice (MVM) infections lead to the appearance of new phosphorylated cellular protein species. This prompted us to investigate whether MVM actively interferes with phosphoinositol‐dependent kinase (PDK)/PKC signalling. The activity, subcellular localization and phosphorylation status of the protein kinases PDK1, PKCη and PKCλ were measured in A9 cells in the presence or absence of MVM infection. Parvovirus infection was found to result in activation of both PDK1 and PKCη, as evidenced by changes in their subcellular distribution and overall (auto)phosphorylation. We show evidence that activation of PKCη by PDK1 is driven by atypical PKCλ. By modifying the hydrophobic motif of PKCη, PKCλ appeared to control docking and consecutive phosphorylation of PKCη's activation‐loop by PDK1, a process that was inhibited in vivo in the presence of a dominant‐negative PKCλ mutant.