Protein kinase D1: a new component in TLR9 signaling.
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-kappaB 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.
Park
Jeoung-Eun
JE
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, USA.
Kim
Young-In
YI
Yi
Ae-Kyung
AK
D000818:Animals; D002478:Cells, Cultured; D018899:CpG Islands; D016207:Cytokines / Q000096:biosynthesis; D004247:DNA / Q000235:genetics; D004789:Enzyme Activation; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases / Q000378:metabolism; D008264:Macrophages / Q000201:enzymology; D051379:Mice; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction; D051217:Toll-Like Receptor 9 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
D016207:Cytokines; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D047428:Protein Kinase Inhibitors; D051217:Toll-Like Receptor 9; D014157:Transcription Factors; D004247:DNA; C089212:protein kinase D; D019061:src-Family Kinases; D053592:Interleukin-1 Receptor-Associated Kinases; C507769:Irak1 protein, mouse; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases