Dual infection system identifies a crucial role for PKA-mediated serine phosphorylation of the EPEC-Tir-injected effector protein in regulating Rac1 function

Brandt S, Kenny B, Rohde M, Martinez-Quiles N, Backert S (2009)

Publication Type: Journal article

Publication year: 2009

Journal

Cellular Microbiology Wiley

Book Volume: 11

Pages Range: 1254-1271

Journal Issue: 8

DOI: 10.1111/j.1462-5822.2009.01330.x

Abstract

Many Gram-negative pathogenic bacteria possess type-III or type-IV secretion systems to inject 'effector' proteins directly into host cells to modulate cellular processes in their favour. A common target is the actin-cytoskeleton linked to the delivery of a single (CagA) effector by Helicobacter pylori and multiple effectors by enteropathogenic Escherichia coli (EPEC) respectively. Here we report co-infection as a powerful strategy for defining effector protein function and mechanisms by which they modulate cellular responses. This is exemplified by our finding that EPEC inhibits H. pylori-induced AGS cell elongation, a disease-related event linked to Rac1 activation. While this inhibitory process is dependent on the translocated Intimin receptor, Tir, and the outer-membrane protein, Intimin, it unexpectedly revealed evidence for Tir signalling independent of Intimin interaction and tyrosine phosphorylation of Tir. Furthermore, the work defined a long awaited role for protein kinase A (PKA)-mediated phosphorylation of Tir at serine-434 and serine-463. Our data are consistent with a model whereby EPEC activates PKA for Tir phosphorylation. Activated PKA then phosphorylates Rac1 at serine-71 associated with reduced GTP-load and inhibited cell elongation. Thus, the co-infection approach is a powerful strategy for defining novel effector function with important implications for characterizing mechanisms and regulatory signalling pathways in bacterial pathogenesis. © 2009 Blackwell Publishing Ltd.

Authors with CRIS profile

Steffen Backert

Involved external institutions

Helmholtz-Zentrum für Infektionsforschung (HZI) DE Germany (DE) Newcastle University GB United Kingdom (GB) Universidad Complutense de Madrid (UCM) ES Spain (ES) Otto-von-Guericke-Universität Magdeburg DE Germany (DE)

How to cite

APA:

Brandt, S., Kenny, B., Rohde, M., Martinez-Quiles, N., & Backert, S. (2009). Dual infection system identifies a crucial role for PKA-mediated serine phosphorylation of the EPEC-Tir-injected effector protein in regulating Rac1 function. Cellular Microbiology, 11(8), 1254-1271. https://doi.org/10.1111/j.1462-5822.2009.01330.x

MLA:

Brandt, Sabine, et al. "Dual infection system identifies a crucial role for PKA-mediated serine phosphorylation of the EPEC-Tir-injected effector protein in regulating Rac1 function." Cellular Microbiology 11.8 (2009): 1254-1271.

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