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Drosophila peptidoglycan recognition protein LC (PGRP-LC) acts as a signal-transducing innate immune receptor
Kwang-Min Choe *,
Hyangkyu Lee, and
Kathryn V. Anderson *, ¶
*Developmental Biology Program, SloanKettering Institute, Memorial SloanKettering Cancer Center, 1275 York Avenue, New York, NY 10021; and Department of Molecular Pharmacology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461
Edited by Frederick M. Ausubel, Harvard Medical School, Boston, MA, and approved November 30, 2004
Received for publication July 9, 2004.
Abstract:Drosophila peptidoglycan recognition protein LC (PGRP-LC), atransmembrane protein required for the response to bacterialinfection, acts at the top of a cytoplasmic signaling cascadethat requires the death-domain protein Imd and an IB kinaseto activate Relish, an NF-B family member. It is not clear howbinding of peptidoglycan to the extracellular domain of PGRP-LCactivates intracellular signaling because its cytoplasmic domainhas no homology to characterized proteins. Here, we demonstratethat PGRP-LC binds Imd and that its cytoplasmic domain is criticalfor its activity, suggesting that PGRP-LC acts as a signal-transducingreceptor. The PGRP-LC cytoplasmic domain is also essential forthe formation of dimers, and results suggest that dimerizationmay be required for receptor activation. The PGRP-LC cytoplasmicdomain can mediate formation of heterodimers between differentPGRP-LC isoforms, thereby potentially expanding the diversityof ligands that can be recognized by the receptor.
Key Words: Imd innate immunity NF-B Relish
Author contributions: K.-M.C. and K.V.A. designed research;K.-M.C. and H.L. performed research; K.-M.C. contributed newreagents/analytic tools; K.-M.C., H.L., and K.V.A. analyzeddata; and K.-M.C. and K.V.A. wrote the paper.
This paper was submitted directly (Track II) to the PNAS office.