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A Conserved p38 MAP Kinase Pathway in Caenorhabditis elegans Innate Immunity
Dennis H. Kim,1*Rhonda Feinbaum,1*Geneviève Alloing,1Fred E. Emerson,1Danielle A. Garsin,1Hideki Inoue,2Miho Tanaka-Hino,2Naoki Hisamoto,2Kunihiro Matsumoto,2Man-Wah Tan,1Frederick M. Ausubel1§
A genetic screen for Caenorhabditis elegans mutants with
enhanced susceptibility to killing by Pseudomonas aeruginosa
ledto the identification of two genes required for pathogen
resistance:sek-1, which encodes a mitogen-activated protein
(MAP) kinasekinase, and nsy-1, which encodes a MAP kinase
kinase kinase. RNAinterference assays and biochemical analysis
established thata p38 ortholog, pmk-1, functions as the
downstream MAP kinaserequired for pathogen defense. These data suggest
that this MAPkinase signaling cassette represents an ancient feature
of innateimmune responses in evolutionarily diverse species.
1 Department of Genetics, Harvard Medical
School, and Department of Molecular Biology, Massachusetts General
Hospital, Boston, MA 02114, USA.
2 Department of
Molecular Biology, Graduate School of Science, Nagoya University and
CREST, Japan Science and Technology Corporation, Chikusa-ku, Nagoya
464-8602, Japan.
*
These authors contributed equally to this work.
Present address: Laboratoire de Biologie Vegetale et
Microbiologie, Universite de Nice-Sophia Antipolis, Parc Valrose 06108Nice Cedex 2, France.
Present address: Department of Genetics, Stanford
University School of Medicine, 300 Pasteur Drive, Room M337, Stanford,
CA94305-5120, USA.
§
To whom correspondence should be addressed. E-mail:
ausubel{at}molbio.mgh.harvard.edu
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