Editors' ChoiceInnate Immunity

PKD’s Gut Reaction

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Science Signaling  21 Apr 2009:
Vol. 2, Issue 67, pp. ec139
DOI: 10.1126/scisignal.267ec139

Protein kinase D (PKD) is a serine/threonine kinase that is recruited to diacylglycerol (DAG) at the plasma membrane, as a consequence of the actions of various isoforms of phospholipase C, where it is phosphorylated and activated by PKC isoforms. Although some functions of PKD have been investigated in vitro, little is known about its physiological roles. The group of Ren et al., who had previously identified DKF-2 as a homolog of PKD in Caenorhabditis elegans, found that a green fluorescent protein (GFP)–tagged form of DKF-2 was primarily localized in the intestines of transgenic worms. Expression of DKF-2-GFP on a wild-type (WT) background improved the survival of C. elegans fed a diet of pathogenic bacteria compared with that of WT worms, whereas deletion of dkf-2 had the reverse effect. In vitro kinase assays showed that pathogenic bacteria stimulated the activity of DKF-2 and that the extent of activation correlated with their pathogenicity. DNA microarray assays showed that active DKF-2 induced the expression of genes that encoded antibacterial peptides and proteins that are important for innate immunity. The expression of most of these genes was dependent on the activity of PMK-1, a C. elegans homolog of p38 mitogen-activated protein kinase. The immune response to pathogenic bacteria in the gut depended on the presence of phosphorylated, activated DKF-2 (rather than unphosphorylated DKF-2, which can act as a scaffold protein), and this was mediated by only one of the three homologs of PKC, TPA-1. Given the conservation of components of innate immunity from worms to humans, this study should stimulate investigation of a role for a DAG-PKC-PKD axis in host defense against bacteria in vertebrates.

M. Ren, H. Feng, Y. Fu, M. Land, C. S. Rubin, Protein kinase D is an essential regulator of C. elegans innate immunity. Immunity 30, 521–532 (2009). [PubMed]

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