Alphaherpesvirus US3-mediated reorganization of the actin cytoskeleton is mediated by group A p21-activated kinases | Zendy

Céline Van den Broeke | Zendy; Maria Radu | Zendy; Matthias Deruelle | Zendy; Hans Nauwynck | Zendy; Clemens Hofmann | Zendy; Zahara M. Jaffer | Zendy; Jonathan Chernoff | Zendy; Herman W. Favoreel | Zendy

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Alphaherpesvirus US3-mediated reorganization of the actin cytoskeleton is mediated by group A p21-activated kinases

Author(s) -

Céline Van den Broeke,

Maria Radu,

Matthias Deruelle,

Hans Nauwynck,

Clemens Hofmann,

Zahara M. Jaffer,

Jonathan Chernoff,

Herman W. Favoreel

Publication year - 2009

Publication title -

proceedings of the national academy of sciences

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 5.011

H-Index - 771

eISSN - 1091-6490

pISSN - 0027-8424

DOI - 10.1073/pnas.0900436106

Subject(s) - pak1 , microbiology and biotechnology , cdc42 , actin cytoskeleton , cytoskeleton , stress fiber , kinase , biology , phosphorylation , actin , rac1 , gtpase , actin remodeling , chemistry , signal transduction , biochemistry , cell , focal adhesion

The US3 protein is a viral serine/threonine kinase that is conserved among all members of the Alphaherpesvirinae. The US3 protein of different alphaherpesviruses causes dramatic alterations in the actin cytoskeleton, such as the disassembly of actin stress fibers and formation of cell projections, which have been associated with increased intercellular virus spread. Here, we find that inhibiting group A p21-activated kinases (PAKs), which are key regulators in Cdc42/Rac1 Rho GTPase signaling pathways, impairs US3-mediated actin alterations. By using PAK1(-/-) and PAK2(-/-) mouse embryo fibroblasts (MEFs), we show that US3-mediated stress fiber disassembly requires PAK2, whereas US3-mediated cell projection formation mainly is mediated by PAK1, also indicating that PAK1 and PAK2 can have different biological effects on the organization of the actin cytoskeleton. In addition, US3 was found to bind and phosphorylate group A PAKs. Lack of group A PAKs in MEFs was correlated with inefficient virus spread. Thus, US3 induces its effect on the actin cytoskeleton via group A PAKs.

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