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Functional diversity of the Drosophila PGRP-LC gene cluster in the response to lipopolysaccharide and peptidoglycan.
Umeå University, Faculty of Medicine, Umeå Centre for Molecular Pathogenesis (UCMP) (Faculty of Medicine). (Dan Hultmark)
Umeå University, Faculty of Medicine, Umeå Centre for Molecular Pathogenesis (UCMP) (Faculty of Medicine). (Dan Hultmark)
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2003 (English)In: J Biol Chem, ISSN 0021-9258, Vol. 278, no 29, 26319-22 p.Article in journal (Refereed) Published
Abstract [en]

The peptidoglycan recognition protein PGRP-LC is a major activator of the imd/Relish pathway in the Drosophila immune response. Three transcripts are generated by alternative splicing of the complex PGRP-LC gene. The encoded transmembrane proteins share an identical intracellular part, but each has a separate extracellular PGRP-domain: x, y, or a. Here we show that two of these isoforms play unique roles in the response to different microorganisms. Using RNA interference in Drosophila mbn-2 cells, we found that PGRP-LCx is the only isoform required to mediate signals from Gram-positive bacteria and purified bacterial peptidoglycan. By contrast, the recognition of Gram-negative bacteria and bacterial lipopolysaccharide requires both PGRP-LCa and LCx. The third isoform, LCy, is expressed at lower levels and may be partially redundant. Two additional PGRP domains in the gene cluster, z and w, are both included in a single transcript of a separate gene, PGRP-LF. Suppression of this transcript does not block the response to any of the microorganisms tested.

Place, publisher, year, edition, pages
2003. Vol. 278, no 29, 26319-22 p.
Keyword [en]
Alternative Splicing, Animals, Carrier Proteins/*genetics, Cell Line, Drosophila/drug effects/*genetics/immunology/microbiology, Drosophila Proteins/*genetics, Genes; Insect/drug effects, Gram-Negative Bacteria/pathogenicity, Gram-Positive Bacteria/pathogenicity, Lipopolysaccharides/pharmacology, Multigene Family/drug effects, Peptidoglycan/pharmacology, RNA Interference
Identifiers
URN: urn:nbn:se:umu:diva-17058DOI: 10.1074/jbc.C300184200PubMedID: 12777387OAI: oai:DiVA.org:umu-17058DiVA: diva2:156731
Available from: 2007-10-28 Created: 2007-10-28Bibliographically approved

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Publisher's full textPubMedhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=12777387&dopt=Citation

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Borge Renberg, KarinHultmark, Dan

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