Protein kinase D1 is essential for MyD88-dependent TLR signaling pathway

Jeoung Eun Park, Young In Kim Hoehamer, Ae-Kyung Yi

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Protein kinase D1 (PKD1) has been shown to be involved in certain MAPK activation and cytokine expression by several TLR ligands. However, the precise physiological role of PKD1 in individual signaling from TLRs has not been fully addressed. In this study, we provide evidence that PKD1 is being activated by TLR ligands, except the TLR3 ligand. PKD1 activation by TLR ligands is dependent on MyD88, IL-1R-associated kinase 4 and 1, but independent of TNF-α receptor-associated factor 6. PKD1-knockdown macrophages and bone marrow-derived dendritic cells revealed that PKD1 is indispensable for the MyD88-dependent ubiquitination of TNF-αreceptor-associated factor 6; activation of TGF-β-activated kinase 1, MAPKs, and transcription factors; and expression of proinflammatory genes induced by TLR ligands, but is not involved in expression of type I IFNs induced by TLR ligands and TRIF-dependent genes induced by TLR3 and TLR4 ligands. These results demonstrate that PKD1 is essential for MyD88-dependent proinflammatory immune responses.

Original languageEnglish (US)
Pages (from-to)6316-6327
Number of pages12
JournalJournal of Immunology
Volume182
Issue number10
DOIs
StatePublished - May 15 2009

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Protein Kinases
Ligands
TNF Receptor-Associated Factor 6
MAP Kinase Kinase 1
Ubiquitination
Dendritic Cells
Transcription Factors
Phosphotransferases
Macrophages
Cytokines
Gene Expression
Genes

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

Protein kinase D1 is essential for MyD88-dependent TLR signaling pathway. / Park, Jeoung Eun; Kim Hoehamer, Young In; Yi, Ae-Kyung.

In: Journal of Immunology, Vol. 182, No. 10, 15.05.2009, p. 6316-6327.

Research output: Contribution to journalArticle

Park, Jeoung Eun ; Kim Hoehamer, Young In ; Yi, Ae-Kyung. / Protein kinase D1 is essential for MyD88-dependent TLR signaling pathway. In: Journal of Immunology. 2009 ; Vol. 182, No. 10. pp. 6316-6327.
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