Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

PNAS 102 (4): 1122-1126

Copyright © 2005 by the National Academy of Sciences.


Drosophila peptidoglycan recognition protein LC (PGRP-LC) acts as a signal-transducing innate immune receptor

Kwang-Min Choe * {dagger}, Hyangkyu Lee {ddagger} §, and Kathryn V. Anderson *, ¶

*Developmental Biology Program, Sloan–Kettering Institute, Memorial Sloan–Kettering Cancer Center, 1275 York Avenue, New York, NY 10021; and {ddagger}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), a transmembrane protein required for the response to bacterial infection, acts at the top of a cytoplasmic signaling cascade that requires the death-domain protein Imd and an I{kappa}B kinase to activate Relish, an NF-{kappa}B family member. It is not clear how binding of peptidoglycan to the extracellular domain of PGRP-LC activates intracellular signaling because its cytoplasmic domain has no homology to characterized proteins. Here, we demonstrate that PGRP-LC binds Imd and that its cytoplasmic domain is critical for its activity, suggesting that PGRP-LC acts as a signal-transducing receptor. The PGRP-LC cytoplasmic domain is also essential for the formation of dimers, and results suggest that dimerization may be required for receptor activation. The PGRP-LC cytoplasmic domain can mediate formation of heterodimers between different PGRP-LC isoforms, thereby potentially expanding the diversity of ligands that can be recognized by the receptor.

Key Words: Imd • innate immunity • NF-{kappa}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 new reagents/analytic tools; K.-M.C., H.L., and K.V.A. analyzed data; and K.-M.C. and K.V.A. wrote the paper.

This paper was submitted directly (Track II) to the PNAS office.

Abbreviations: PGRP, peptidoglycan-recognition protein; PAMP, pathogen-associated molecular pattern; TLR, Toll-like receptor; PRR, pattern-recognition receptor.

{dagger} Present address: Department of Neurobiology, Stanford University School of Medicine, 299 Campus Drive West, Stanford, CA 94305.

§ Present address: Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305.

To whom correspondence should be addressed. E-mail: k-anderson{at}

© 2005 by The National Academy of Sciences of the USA

The Drosophila Imd Signaling Pathway.
H. Myllymaki, S. Valanne, and M. Ramet (2014)
J. Immunol. 192, 3455-3462
   Abstract »    Full Text »    PDF »
Tissue- and Ligand-Specific Sensing of Gram-Negative Infection in Drosophila by PGRP-LC Isoforms and PGRP-LE.
C. Neyen, M. Poidevin, A. Roussel, and B. Lemaitre (2012)
J. Immunol. 189, 1886-1897
   Abstract »    Full Text »    PDF »
Ubiquitylation of the initiator caspase DREDD is required for innate immune signalling.
A. Meinander, C. Runchel, T. Tenev, L. Chen, C.-H. Kim, P. S. Ribeiro, M. Broemer, F. Leulier, M. Zvelebil, N. Silverman, et al. (2012)
EMBO J. 31, 2770-2783
   Abstract »    Full Text »    PDF »
Drosophila as a model system to unravel the layers of innate immunity to infection.
I. Kounatidis and P. Ligoxygakis (2012)
Open Bio 2, 120075
   Abstract »    Full Text »    PDF »
Functional Conservation and Innovation of Amphioxus RIP1-Mediated Signaling in Cell Fate Determination.
J. Li, S. Yuan, L. Qi, S. Huang, G. Huang, M. Yang, L. Xu, Y. Li, R. Zhang, Y. Yu, et al. (2011)
J. Immunol. 187, 3962-3971
   Abstract »    Full Text »    PDF »
The Drosophila peptidoglycan-recognition protein LF interacts with peptidoglycan-recognition protein LC to downregulate the Imd pathway.
N. Basbous, F. Coste, P. Leone, R. Vincentelli, J. Royet, C. Kellenberger, and A. Roussel (2011)
EMBO Rep. 12, 327-333
   Abstract »    Full Text »    PDF »
NF-{kappa}B in the Immune Response of Drosophila.
C. Hetru and J. A. Hoffmann (2009)
Cold Spring Harb Perspect Biol 1, a000232
   Abstract »    Full Text »    PDF »
Elevated CO2 suppresses specific Drosophila innate immune responses and resistance to bacterial infection.
I. T. Helenius, T. Krupinski, D. W. Turnbull, Y. Gruenbaum, N. Silverman, E. A. Johnson, P. H. S. Sporn, J. I. Sznajder, and G. J. Beitel (2009)
PNAS 106, 18710-18715
   Abstract »    Full Text »    PDF »
Elimination of plasmatocytes by targeted apoptosis reveals their role in multiple aspects of the Drosophila immune response.
B. Charroux and J. Royet (2009)
PNAS 106, 9797-9802
   Abstract »    Full Text »    PDF »
Pirk Is a Negative Regulator of the Drosophila Imd Pathway.
A. Kleino, H. Myllymaki, J. Kallio, L.-M. Vanha-aho, K. Oksanen, J. Ulvila, D. Hultmark, S. Valanne, and M. Ramet (2008)
J. Immunol. 180, 5413-5422
   Abstract »    Full Text »    PDF »
Infection-induced proteolysis of PGRP-LC controls the IMD activation and melanization cascades in Drosophila.
R. L. Schmidt, T. R. Trejo, T. B. Plummer, J. L. Platt, and A. H. Tang (2008)
FASEB J 22, 918-929
   Abstract »    Full Text »    PDF »
Toll and IMD Pathways Synergistically Activate an Innate Immune Response in Drosophila melanogaster.
T. Tanji, X. Hu, A. N. R. Weber, and Y. T. Ip (2007)
Mol. Cell. Biol. 27, 4578-4588
   Abstract »    Full Text »    PDF »
The Drosophila Inhibitor of Apoptosis Protein DIAP2 Functions in Innate Immunity and Is Essential To Resist Gram-Negative Bacterial Infection.
F. Leulier, N. Lhocine, B. Lemaitre, and P. Meier (2006)
Mol. Cell. Biol. 26, 7821-7831
   Abstract »    Full Text »    PDF »
Genetic Variation in Drosophila melanogaster Resistance to Infection: A Comparison Across Bacteria.
B. P. Lazzaro, T. B. Sackton, and A. G. Clark (2006)
Genetics 174, 1539-1554
   Abstract »    Full Text »    PDF »
Host PGRP Gene Expression and Bacterial Release in Endosymbiosis of the Weevil Sitophilus zeamais.
C. Anselme, A. Vallier, S. Balmand, M.-O. Fauvarque, and A. Heddi (2006)
Appl. Envir. Microbiol. 72, 6766-6772
   Abstract »    Full Text »    PDF »
Structure of tracheal cytotoxin in complex with a heterodimeric pattern-recognition receptor..
C.-I Chang, Y. Chelliah, D. Borek, D. Mengin-Lecreulx, and J. Deisenhofer (2006)
Science 311, 1761-1764
   Abstract »    Full Text »    PDF »
Structural Basis for Preferential Recognition of Diaminopimelic Acid-type Peptidoglycan by a Subset of Peptidoglycan Recognition Proteins.
J.-H. Lim, M.-S. Kim, H.-E. Kim, T. Yano, Y. Oshima, K. Aggarwal, W. E. Goldman, N. Silverman, S. Kurata, and B.-H. Oh (2006)
J. Biol. Chem. 281, 8286-8295
   Abstract »    Full Text »    PDF »
Dual strategies for peptidoglycan discrimination by peptidoglycan recognition proteins (PGRPs).
C. P. Swaminathan, P. H. Brown, A. Roychowdhury, Q. Wang, R. Guan, N. Silverman, W. E. Goldman, G.-J. Boons, and R. A. Mariuzza (2006)
PNAS 103, 684-689
   Abstract »    Full Text »    PDF »
The Role of Ubiquitination in Drosophila Innate Immunity.
R. Zhou, N. Silverman, M. Hong, D. S. Liao, Y. Chung, Z. J. Chen, and T. Maniatis (2005)
J. Biol. Chem. 280, 34048-34055
   Abstract »    Full Text »    PDF »
Inhibitor of apoptosis 2 and TAK1-binding protein are components of the Drosophila Imd pathway.
A. Kleino, S. Valanne, J. Ulvila, J. Kallio, H. Myllymaki, H. Enwald, S. Stoven, M. Poidevin, R. Ueda, D. Hultmark, et al. (2005)
EMBO J. 24, 3423-3434
   Abstract »    Full Text »    PDF »
Structure of the ectodomain of Drosophila peptidoglycan-recognition protein LCa suggests a molecular mechanism for pattern recognition.
C.-I Chang, K. Ihara, Y. Chelliah, D. Mengin-Lecreulx, S. Wakatsuki, and J. Deisenhofer (2005)
PNAS 102, 10279-10284
   Abstract »    Full Text »    PDF »
Ligand-induced dimerization of Drosophila peptidoglycan recognition proteins in vitro.
P. Mellroth, J. Karlsson, J. Hakansson, N. Schultz, W. E. Goldman, and H. Steiner (2005)
PNAS 102, 6455-6460
   Abstract »    Full Text »    PDF »
Biography of Kathryn V. Anderson.
B. Trivedi (2005)
PNAS 102, 5910-5912
   Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882