Protein kinase D is an essential regulator of C. elegans innate immunity.
Protein kinase D (PKD) mediates signal transduction downstream from phospholipase C and diacylglycerol (DAG). PKDs are activated by hormones and stress in cell lines, but little is known about PKD functions and regulation in vivo. Here, we show that DKF-2, a C. elegans PKD, regulates innate immunity. Animals lacking DKF-2 were hypersensitive to killing by bacteria that are pathogens of C. elegans and humans. DKF-2 induced 85 mRNAs, which encode antimicrobial peptides and proteins that sustain intestinal epithelium. Induction of immune effector mRNAs by DKF-2 proceeded via PMK-1 (p38 Map-kinase)-dependent and -independent pathways. TPA-1, a PKCdelta homolog, regulated activation and functions of DKF-2 in vivo. Therefore, DKF-2 provides a molecular link that couples DAG signaling to regulation of immunity. This intersection between DAG-TPA-1-DKF-2 and PMK-1 pathways enables integrated immune responses to multiple stimuli. Thus, a PKD mobilizes activation of host immune defenses against pathogens by previously unappreciated signaling pathways and mechanisms.
Ren
Min
M
Department of Molecular Pharmacology, Atran Laboratories, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Feng
Hui
H
Fu
Ya
Y
Land
Marianne
M
Rubin
Charles S
CS
D000818:Animals; D018407:Bacterial Physiological Phenomena; D017173:Caenorhabditis elegans / Q000201:enzymology* / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate; D007422:Intestines / Q000276:immunology; D046228:Microarray Analysis; D011493:Protein Kinase C / Q000235:genetics / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
D029742:Caenorhabditis elegans Proteins; D012333:RNA, Messenger; C524695:DKF-2 protein, C elegans; D011493:Protein Kinase C