The MAPK-activated kinase Rsk controls an acute Toll-like receptor signaling response in dendritic cells and is activated through two distinct pathways.
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.
Zaru
Rossana
R
Division of Cell Biology and Immunology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Ronkina
Natalia
N
Gaestel
Matthias
M
Arthur
J Simon C
JS
Watts
Colin
C
D000595:Amino Acid Sequence; D000818:Animals; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D004789:Enzyme Activation / Q000276:immunology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000276:immunology / Q000378:metabolism; D015151:Immunoblotting; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology / Q000378:metabolism
D007527:Isoenzymes; D051193:Toll-Like Receptors; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases