Expression of herpes simplex virus type 2 US3 affects the Cdc42/Rac pathway and attenuates c-Jun N-terminal kinase activation

T. Murata, F. Goshima, T. Daikoku, H. Takakuwa, Y. Nishiyama

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Background: Although the US3 gene product of herpes simplex virus (HSV) has been identified as a serine/threonine protein kinase (PK), the functions are poorly understood. Results: We found that US3 PK of HSV-2 induced disruption of actin filaments, cell rounding and accumulation of binucleate cells in HEp2 cells. Cell rounding was abrogated by expression of either kinase-dead forms of US3 PK or a mutant protein lacking the acidic cluster in the kinase regulatory domain. Co-expression of dominant active forms of Cdc42/Rac inhibited cell rounding, suggesting that a signal transduction pathway involving Cdc42/Rac may play a role in the morphological changes induced by the kinase. Cdc42 and Rac, members of the Rho family of small GTPases, function as molecular switches changing actin cytoskeletal organization, influencing transcription and controlling apoptotic cell death. By computed homology search, we noticed significant similarities between US3 PK and p21-activated kinase (PAK), which is activated by the Cdc42 or Rac. We also found that the expression of US3 suppressed the activation of c-Jun N-terminal kinase (JNK), a kinase that is downstream of PAK. Conclusions: These observations suggest that the US3 PK affects the Cdc42/Rac pathway and can act as an upstream suppressor of JNK in the stress-activated signalling pathway.

Original languageEnglish
Pages (from-to)1017-1027
Number of pages11
JournalGenes to Cells
Volume5
Issue number12
DOIs
Publication statusPublished - 01-01-2000
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Genetics
  • Cell Biology

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