Article abstract

Nature Immunology 8, 1227 - 1235 (2007)
Published online: 30 September 2007 | Corrected online: 16 November 2007 | doi:10.1038/ni1517



There is a Corrigendum (January 2008) associated with this Article.

The MAPK-activated kinase Rsk controls an acute Toll-like receptor signaling response in dendritic cells and is activated through two distinct pathways

Rossana Zaru1, Natalia Ronkina2, Matthias Gaestel2, J Simon C Arthur3 & Colin Watts1

Most dendritic cell (DC) responses to Toll-like receptor (TLR) ligands depend on the activation of mitogen-activated protein kinases (MAPKs), but the contributions of the many MAPK-activated kinases (MKs) that act 'downstream' of the MAPKs Erk and p38 are not known. Here we sought to determine which MKs are required for acute TLR-driven, MAPK-dependent DC endocytic responses. Two specific and structurally different inhibitors of the MK Rsk suppressed TLR-induced endocytosis, thus defining in DCs a specific requirement for MKs in TLR responses. In addition, we identify in DCs a previously unknown configuration of the MAPK system whereby Rsk is activated not only by Erk but also by p38 through the intermediates MK2 and MK3. Thus, in DCs, p38 contributes to the activation of all known MK families.

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  1. Division of Cell Biology and Immunology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
  2. Department of Biochemistry, Medical School Hanover, 30625 Hanover, Germany.
  3. Medical Research Council Protein Phosphorylation Unit, Sir James Black Centre, University of Dundee, DD1 5EH, UK.

Correspondence to: Colin Watts1 e-mail: c.watts@dundee.ac.uk

* In the version of this article initially published, the Author Contributions section was incorrect. The correct author contributions are as follows: R.Z and C.W designed the study, interpreted the data and wrote the manuscript; R.Z. did the experiments; N.R. and M.G. provided MK2-null mice and generated embryonic stem cells carrying a targeted allele of MK3; J.S.C.A. provided advice and MSK1-MSK2-null mice and generated MK3-null mice from the MK3 embryonic stem cells provided by N.R. and M.G. The error has been corrected in the PDF version of the article.

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