source: http://cegg.unige.ch/insecta/immunodb/expert

IMDPATHs: IMD Pathway Members
Summary

Sang Woon Shin, Guowu Bian, Kanwal Alvarez, and Alexander Raikhel 

Department of Entomology and the Institute for Integrative Genome Biology, University of California, Riverside California 92521, USA 

Innate immune signal transduction pathways connect the extracellular recognition and amplification signals with intracellular transcriptional activation of a large repertoire of immune molecules including AMPs. The insect innate immune system relies on two major signaling pathways, Toll and Imd pathways. In Drosophila, the Toll pathway activates antifungal defenses and mediates response to Gram-positive (+) bacteria infection, whereas the IMD pathway is activated by Gram-negative (-) bacteria infection [Brennan & Anderson 2004]. 

The IMD pathway culminates in the activation of another NF-kappaB transcription factor, Relish, which in Drosophila activates AMPs such as Diptericin. Signaling by this pathway mimics the mammalian TNFR1 (tumor necrosis factor receptor) cascade. IMD, a death domain protein that is most similar to the mammalian receptor interacting protein 1 (RIP1), interacts with the cytoplasmic domain of the receptor PGRP-LC [Choe et al. 2005]. A central step resulting in the activation of TAK1, a MAP3K, is its ubiquitination by Drosophila Ubc13/Uev1A ubiquitin-conjugating complex [Zhu et al. 2005]. TAB2 has been suggested to function in a step between IMD and TAK1 [Zhuang et al. 2006]. However, the requirement of TAK1 in Relish activation has been questioned [Delaney et al. 2006]. Drosophila FADD acts downstream of IMD linking it with DREDD [Naitza et al. 2002]. Drosophila IKK complex (IKKb/IKKg) and DREDD, a Drosophila homologue of mammalian Caspase 8, are required for the signal-dependent phosphorylation and endoproteolytic cleavage of Relish [St�ven et al. 2003]. After endoproteolysis of Relish, the N-terminal NF-kappaB module translocates to the nucleus where it drives the expression of immune genes while the C-terminal IkB domain remains in the cytoplasm [St�ven et al. 2003]. The genome sequences of Ae. aegypti and An. gambiae contain 1:1 orthologs of Drosophila IMD pathway components: Imd, FADD, TAK1, DREDD (CaspaseL1) and IKKg (IKK2). Two genomic loci of Ae. aegypti encode almost identical proteins, which are orthologs of Drosophila IKKb (IKK1).