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

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Organization
Abstract
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.
Keywords
viral kinase, projections, PSEUDORABIES VIRUS US3, STRESS FIBER BREAKDOWN, NEF-ASSOCIATED KINASE, TO-CELL SPREAD, VACCINIA VIRUS, RHO-GTPASES, F11L-MEDIATED INHIBITION, INFECTED-CELLS, stress fibers, Rho GTPase signaling, herpesvirus, ALPHA-PAK, MEMBRANE NANOTUBES

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MLA
Van den Broeke, Celine, Maria Radu, Matthias Deruelle, et al. “Alphaherpesvirus US3-mediated Reorganization of the Actin Cytoskeleton Is Mediated by Group A P21-activated Kinases.” PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 106.21 (2009): 8707–8712. Print.
APA
Van den Broeke, C., Radu, M., Deruelle, M., Nauwynck, H., Hofmann, C., Jaffer, Z. M., Chernoff, J., et al. (2009). Alphaherpesvirus US3-mediated reorganization of the actin cytoskeleton is mediated by group A p21-activated kinases. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 106(21), 8707–8712.
Chicago author-date
Van den Broeke, Celine, Maria Radu, Matthias Deruelle, Hans Nauwynck, Clemens Hofmann, Zahara M Jaffer, Jonathan Chernoff, and Herman Favoreel. 2009. “Alphaherpesvirus US3-mediated Reorganization of the Actin Cytoskeleton Is Mediated by Group A P21-activated Kinases.” Proceedings of the National Academy of Sciences of the United States of America 106 (21): 8707–8712.
Chicago author-date (all authors)
Van den Broeke, Celine, Maria Radu, Matthias Deruelle, Hans Nauwynck, Clemens Hofmann, Zahara M Jaffer, Jonathan Chernoff, and Herman Favoreel. 2009. “Alphaherpesvirus US3-mediated Reorganization of the Actin Cytoskeleton Is Mediated by Group A P21-activated Kinases.” Proceedings of the National Academy of Sciences of the United States of America 106 (21): 8707–8712.
Vancouver
1.
Van den Broeke C, Radu M, Deruelle M, Nauwynck H, Hofmann C, Jaffer ZM, et al. Alphaherpesvirus US3-mediated reorganization of the actin cytoskeleton is mediated by group A p21-activated kinases. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 2009;106(21):8707–12.
IEEE
[1]
C. Van den Broeke et al., “Alphaherpesvirus US3-mediated reorganization of the actin cytoskeleton is mediated by group A p21-activated kinases,” PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 106, no. 21, pp. 8707–8712, 2009.
@article{749184,
  abstract     = {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.},
  author       = {Van den Broeke, Celine and Radu, Maria and Deruelle, Matthias and Nauwynck, Hans and Hofmann, Clemens and Jaffer, Zahara M and Chernoff, Jonathan and Favoreel, Herman},
  issn         = {0027-8424},
  journal      = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
  keywords     = {viral kinase,projections,PSEUDORABIES VIRUS US3,STRESS FIBER BREAKDOWN,NEF-ASSOCIATED KINASE,TO-CELL SPREAD,VACCINIA VIRUS,RHO-GTPASES,F11L-MEDIATED INHIBITION,INFECTED-CELLS,stress fibers,Rho GTPase signaling,herpesvirus,ALPHA-PAK,MEMBRANE NANOTUBES},
  language     = {eng},
  number       = {21},
  pages        = {8707--8712},
  title        = {Alphaherpesvirus US3-mediated reorganization of the actin cytoskeleton is mediated by group A p21-activated kinases},
  url          = {http://dx.doi.org/10.1073/pnas.0900436106},
  volume       = {106},
  year         = {2009},
}

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