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.
Department of Molecular Pharmacology, Atran Laboratories, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Min
M
Ren
Hui
H
Feng
Ya
Y
Fu
Marianne
M
Land
Charles S
CS
Rubin
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