Protein kinase D1 and D2 are involved in chemokine release induced by toll-like receptors 2, 4, and 5.
The protein kinase D (PKD) family consists of three serine-threonine kinases involved in cellular proliferation, motility, and apoptosis. We previously reported that human toll-like receptor 5 (TLR5) contains a consensus PKD phosphorylation site. Flagellin stimulation of cells activated PKD1, and inhibition of PKD1 reduced flagellin-induced interleukin-8 (IL-8) production in epithelial cells. In the current work, we examined PKD1 and PKD2 involvement downstream of TLR5, TLR4 and TLR2. We found that inhibition of either kinase with shRNA reduced IL-8 and CCL20 release due to TLR4 and TLR2 agonists to a similar extent as previously reported for TLR5. PKD1 and PKD2 inhibition reduced NF-kappaB activity but not MAPK activation. These results demonstrate that both PKD1 and PKD2 are required for inflammatory responses following TLR2, TLR4, or TLR5 activation, although PKD1 is more strongly involved. These kinases likely act downstream of the TLRs themselves to facilitate NF-kappaB activation but not MAP kinase phosphorylation.
Steiner
Theodore S
TS
Division of Infectious Diseases, Department of Medicine, University of British Columbia, Rm. D452 HP East, VGH, 2733 Heather St., Vancouver, BC, Canada V5Z 3J5. tsteiner@interchange.ubc.ca
Ivison
Sabine M
SM
Yao
Yu
Y
Kifayet
Arnawaz
A
D018938:Caco-2 Cells; D054418:Chemokine CCL20 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D003001:Cloning, Molecular; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005408:Flagellin / Q000276:immunology / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011493:Protein Kinase C / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000091283:Protein Kinase D2; D011494:Protein Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D051193:Toll-Like Receptors / Q000378:metabolism
D054418:Chemokine CCL20; D016209:Interleukin-8; D016328:NF-kappa B; D000091283:Protein Kinase D2; D034741:RNA, Small Interfering; D051193:Toll-Like Receptors; D005408:Flagellin; D011494:Protein Kinases; C089212:protein kinase D; D011493:Protein Kinase C