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Protein Kinase D1: A New Component in TLR9 Signaling¹

Jeoung-Eun Park^*, Young-In Kim^* and Ae-Kyung Yi^2,*,

^* Children’s Foundation Research Center at Le Bonheur Children’s Medical Center and Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38103; and Department of Molecular Sciences, University of Tennessee Health Science Center, Memphis, TN 38163

Protein kinase D1 (PKD1) is expressed ubiquitously and regulates diverse cellular processes such as oxidative stress, gene expression, cell survival, and vesicle trafficking. However, the presence and function of PKD1 in monocytic cells are currently unknown. In this study, we provide evidence that PKD1 is involved in TLR9 signaling in macrophages. Class B-type CpG DNA (CpG-B DNA) induced activation of PKD1 via a pathway that is dependent on endosomal pH, TLR9, MyD88, and IL-1R-associated kinase 1 in macrophages. Upon CpG-B DNA stimulation, PKD1 interacted with the TLR9/MyD88/IL-1R-associated kinase/TNFR-associated factor 6 complex. Knockdown of PKD1 revealed that PKD1 is required for activation of NF-B and MAPKs, and subsequent expression of cytokines in response to CpG-B DNA. Our findings identify PKD1 as a key signaling modulator in TLR9-mediated macrophage activation.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ A.-K.Y. was supported by the Children’s Foundation Research Center at Le Bonheur Children’s Medical Center, and grants from the National Institutes of Health (AI053137, AR47757) and the Children’s Foundation of Memphis. J.-E.P. was supported by a grant from Le Bonheur Children’s Medical Center. Y.-I.K. was supported by a Postdoctoral Fellowship from the Korea Research Foundation (KRF-2005-214-E00045) and a grant from Le Bonheur Children’s Medical Center. Animal experiments were supported in part by a Transgenic Mice Program grant from the Children’s Foundation of Memphis.

² Address correspondence and reprint requests to Dr. Ae-Kyung Yi, Department of Pediatrics, University of Tennessee Health Science Center, 50 North Dunlap Street, Room 315, Memphis, TN 38103. E-mail address: ayi{at}utmem.edu

³ Abbreviations used in this paper: PRR, pattern recognition receptor; IRF, IFN regulatory factor; IRAK, IL-1R-associated kinase; TRAF, TNFR-associated factor; ROS, reactive oxygen species; PKD, protein kinase D; PLC, phospholipase C; PKC, protein kinase C; DC, dendritic cell; KC, Kupffer cell; cDC, conventional DC; pDC, plasmacytoid DC; ODN, oligodeoxynucleotide; S-ODN, nuclease-resistant phosphorothioate ODN; EC, E. coli; CT, calf thymus; PTK, protein tyrosine kinase; mCsk, membrane-targeted form of C-terminal Src kinase; TIR, Toll/IL-1R; shRNA, small hairpin interfering RNA.

This article has been cited by other articles:

				J.-E. Park, Y.-I. Kim, and A.-K. Yi Protein Kinase D1 Is Essential for MyD88-Dependent TLR Signaling Pathway J. Immunol., May 15, 2009; 182(10): 6316 - 6327. [Abstract] [Full Text] [PDF]