Localization of ERK/MAP kinase is regulated by the alphaherpesvirus tegument protein Us2
| Autor: | Bruce W. Banfield, Jessica A. Randall, Christine M. Calton, Mathew G. Lyman |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
MAPK/ERK pathway
Immunology Biology Virus Replication Microbiology 3T3 cells Cell membrane Enzyme activator Mice Viral Envelope Proteins Virology Two-Hybrid System Techniques Nitriles medicine Butadienes Animals Humans Enzyme Inhibitors Extracellular Signal-Regulated MAP Kinases Sequence Deletion Pseudorabies Base Sequence Kinase Cell Membrane Cytoplasmic Vesicles Virion Molecular biology Herpesvirus 1 Suid Transport protein Virus-Cell Interactions Enzyme Activation Protein Transport medicine.anatomical_structure Viral replication Insect Science Mitogen-activated protein kinase biology.protein NIH 3T3 Cells |
| Zdroj: | Journal of virology. 80(14) |
| ISSN: | 0022-538X |
| Popis: | Many different viruses activate the extracellular signal-regulated kinase (ERK)/mitogen-activated protein (MAP) kinase signaling pathway during infection and require ERK activation for the efficient execution of their replication programs. Despite these findings, no virus-encoded proteins have been identified that directly modulate ERK activities. In an effort to determine the function of a conserved alphaherpesvirus structural protein called Us2, we screened a yeast two-hybrid library derived from NIH 3T3 cells and identified ERK as a Us2-interacting protein. Our studies indicate that Us2 binds to ERK in virus-infected cells, mediates the incorporation of ERK into the virion, and inhibits the activation of ERK nuclear substrates. The association of Us2 with ERK leads to the sequestration of ERK at the plasma membrane and to a perinuclear vesicular compartment, thereby keeping ERK out of the nucleus. Us2 can bind to activated ERK, and the data suggest that Us2 does not inhibit ERK enzymatic activity. The treatment of cells with U0126, a specific inhibitor of ERK activation, resulted in a substantial delay in the release of virus from infected cells that was more pronounced with a virus deleted for Us2 than with parental and repaired strains, suggesting that both ERK and Us2 activities are required for efficient virus replication. This study highlights an additional complexity to the activation of ERK by viruses, namely, that localization of active ERK can be altered by virus-encoded proteins. |
| Databáze: | OpenAIRE |
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