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PLoS One. 2010 Oct 5;5(10). pii: e13165. doi: 10.1371/journal.pone.0013165.

Yersinia virulence factor YopM induces sustained RSK activation by interfering with dephosphorylation.

Author information

1
Institute of Medical Microbiology, Virology and Hygiene, University Medical Center Eppendorf, Hamburg, Germany. jbaltzer@mta.ca

Abstract

BACKGROUND:

Pathogenic yersiniae inject several effector proteins (Yops) into host cells, which subverts immune functions and enables the bacteria to survive within the host organism. YopM, whose deletion in enteropathogenic yersiniae results in a dramatic loss of virulence, has previously been shown to form a complex with and activate the multifunctional kinases PKN2 and RSK1 in transfected cells.

METHODOLOGY/PRINCIPAL FINDINGS:

In a near physiological approach with double-affinity-tagged YopM being translocated into the macrophage cell line J774A.1 via the natural type three secretion system of Yersinia we verified the interaction of YopM with PKN2 and RSK1 and detected association with additional PKN and RSK isoforms. In transfected and infected cells YopM induced sustained phosphorylation of RSK at its activation sites serine-380 and serine-221 even in the absence of signalling from its upstream kinase ERK1/2, suggesting inhibition of dephosphorylation. ATP-depletion and in vitro assays using purified components directly confirmed that YopM shields RSK isoforms from phosphatase activity towards serines 380 and 221.

CONCLUSIONS/SIGNIFICANCE:

Our study suggests that during Yersinia infection YopM induces sustained activation of RSK by blocking dephosphorylation of its activatory phosphorylation sites. This may represent a novel mode of action of a bacterial virulence factor.

PMID:
20957203
PMCID:
PMC2950144
DOI:
10.1371/journal.pone.0013165
[Indexed for MEDLINE]
Free PMC Article

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