Protein kinase Cdelta binds TIRAP/Mal to participate in TLR signaling

Miho Kubo-Murai; Kaoru Hazeki; Naoe Sukenobu; Kyoko Yoshikawa; Kiyomi Nigorikawa; Kazumi Inoue; Toshiyoshi Yamamoto; Misako Matsumoto; Tsukasa Seya; Norimitsu Inoue; Osamu Hazeki

doi:10.1016/j.molimm.2006.11.005

Protein kinase Cdelta binds TIRAP/Mal to participate in TLR signaling

Mol Immunol. 2007 Mar;44(9):2257-64. doi: 10.1016/j.molimm.2006.11.005. Epub 2006 Dec 11.

Authors

Miho Kubo-Murai¹, Kaoru Hazeki, Naoe Sukenobu, Kyoko Yoshikawa, Kiyomi Nigorikawa, Kazumi Inoue, Toshiyoshi Yamamoto, Misako Matsumoto, Tsukasa Seya, Norimitsu Inoue, Osamu Hazeki

Affiliation

¹ The Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan.

PMID: 17161867
DOI: 10.1016/j.molimm.2006.11.005

Abstract

Toll-like receptor (TLR) family members recognize specific molecular patterns within pathogens. Signaling through TLRs results in a proximal event that involves direct binding of adaptor proteins to the receptors. We observed that TIRAP/Mal, an adaptor protein for TLR2 and TLR4, binds protein kinase Cdelta (PKCdelta). TIRAP/Mal GST-fusion protein and a TIRAP/Mal antibody were able to precipitate PKCdelta from rat peritoneal macrophage and THP1 cell lysates. Truncation mutants of TIRAP/Mal showed that the TIR domain of TIRAP/Mal is responsible for binding. TLR2- and TLR4-mediated phosphorylation of p38 MAPK, IKK, and IkappaB in RAW264.7 cells were abolished by depletion of PKCdelta. These results suggest that PKCdelta binding to TIRAP/Mal promotes TLR signaling events.

MeSH terms

Animals
Enzyme Activation / drug effects
Female
Glutathione Transferase / metabolism
Humans
I-kappa B Kinase / metabolism
Lipopolysaccharides / pharmacology
Membrane Glycoproteins / chemistry
Membrane Glycoproteins / metabolism*
Mice
Myeloid Differentiation Factor 88 / metabolism
NF-kappa B / metabolism
Protein Binding / drug effects
Protein Kinase C / antagonists & inhibitors
Protein Kinase C-delta / antagonists & inhibitors
Protein Kinase C-delta / metabolism*
Protein Kinase Inhibitors / pharmacology
Protein Structure, Tertiary / drug effects
Rats
Receptors, Interleukin-1 / chemistry
Receptors, Interleukin-1 / metabolism*
Recombinant Fusion Proteins / metabolism
Signal Transduction* / drug effects
Toll-Like Receptors / immunology
Toll-Like Receptors / metabolism*
p38 Mitogen-Activated Protein Kinases / metabolism

Substances

Lipopolysaccharides
Membrane Glycoproteins
Myeloid Differentiation Factor 88
NF-kappa B
Protein Kinase Inhibitors
Receptors, Interleukin-1
Recombinant Fusion Proteins
TIRAP protein, human
Toll-Like Receptors
Glutathione Transferase
protein kinase C eta
I-kappa B Kinase
Protein Kinase C
Protein Kinase C-delta
p38 Mitogen-Activated Protein Kinases