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

Rossana Zaru1, Natalia Ronkina, Matthias Gaestel

  • 1Division of Cell Biology and Immunology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.

Nature Immunology
|October 2, 2007
PubMed

Insights

Mitogen-activated protein kinases (MAPKs) control dendritic cell (DC) Toll-like receptor (TLR) responses. This study reveals Rsk, a MAPK-activated kinase (MK), is crucial for TLR-driven DC endocytosis and activated by both Erk and p38 pathways.

Area of Science:

  • Immunology
  • Cell Biology
  • Signal Transduction

Background:

  • Dendritic cell (DC) activation by Toll-like receptor (TLR) ligands largely relies on mitogen-activated protein kinase (MAPK) signaling pathways.
  • The specific roles of MAPK-activated kinases (MKs) downstream of Erk and p38 in these DC responses remain largely uncharacterized.

Purpose of the Study:

  • To investigate the requirement of specific MKs in acute TLR-driven and MAPK-dependent DC endocytic responses.
  • To elucidate the upstream signaling pathways regulating MK activation in DCs.

Main Methods:

  • Utilized specific inhibitors targeting the MK Rsk to assess its role in TLR-induced endocytosis in DCs.
  • Investigated the activation configurations of the MAPK signaling system in DCs.

Main Results:

  • Inhibition of Rsk significantly suppressed TLR-induced endocytosis in DCs, establishing a critical role for MKs in TLR responses.
  • Identified a novel signaling mechanism where Rsk is activated by both Erk and p38 MAPKs in DCs.
  • Demonstrated that p38 MAPK, via intermediates MK2 and MK3, contributes to the activation of all known MK families in DCs.

Conclusions:

  • MAPK-activated kinases, particularly Rsk, are essential for TLR-mediated endocytosis in dendritic cells.
  • The p38 MAPK pathway plays a broader role in activating downstream MKs, including Rsk, in DCs than previously understood.

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