Toll, IMD, JAK/STAT pathways for immune response to pathogens (WP3830)

Drosophila melanogaster

Yeast, fungi, virus, and lysine-type peptidoglycan (k-type PGN) signal proteins persephone (psh) and GRASS in the Toll Pathway. These proteins signal downstream to sphinx1/2, spheroide, and spirit which leads to activation of Spatzle (spz). Spz binds to Toll which activates death domain-containing molecules (MyD88, Tube, Pelle). Pellino ubiquinates Pelle which allows TRAF to activate DIF which activates Dorsal facilitated by the ubiquitination of cactus. Dorsal translocates to nucleus to upregulate immune genes. The IMD pathway is activated by mono-diaminopimelic acid-type peptidoglycans (DAP-type PGN) that starts a cascade of activation of Fadd, Dredd, Tak1/Tab2 coomplex and leads to the activation, translocation, and effector gene promotion of Relish. The JAK/STAT pathway is activated by Virus and unpaired gene particles binding to dome/JAK/STAT complex leading to the activation of the STAT complex which translocates to the nucleus to promote transcription of effector genes. This pathway was taken from Figure 2A of Severo et al.


AAR&Co , Marianthi Kalafati , Kristina Hanspers , Martina Summer-Kutmon , and Eric Weitz


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Drosophila melanogaster



Pathway Ontology

altered transcription pathway signaling pathway


Label Type Compact URI Comment
STAT GeneProduct uniprot:Q24151
nec GeneProduct ensembl:FBgn0002930
PGRP-SC GeneProduct ensembl:FBgn0043576 PGRP-SC Not Specified
psh GeneProduct ensembl:FBgn0030926
Dif GeneProduct ensembl:FBgn0011274
IkkB GeneProduct uniprot:Q9VEZ5
spirit GeneProduct ensembl:FBgn0030051
spheroide GeneProduct ensembl:FBgn0030774
PGRP-SD GeneProduct ensembl:FBgn0035806
PGRP-LB GeneProduct ensembl:FBgn0037906
Tab2 GeneProduct ensembl:FBgn0086358
Myd88 GeneProduct ensembl:FBgn0033402
sphinx1 GeneProduct ensembl:FBgn0052383
STAT GeneProduct uniprot:Q24151
sphinx2 GeneProduct ensembl:FBgn0052382
imd GeneProduct ensembl:FBgn0013983
TRAF2 GeneProduct uniprot:Q9XYQ9
grass GeneProduct ensembl:FBgn0039494
Socs GeneProduct ensembl:FBgn0030869 Socs Not Specified
SPE GeneProduct ensembl:FBgn0039102
PGRP-LC GeneProduct ensembl:FBgn0035976
Tak1 GeneProduct ensembl:FBgn0026323
PGRP-SA GeneProduct ensembl:FBgn0030310
dome GeneProduct ensembl:FBgn0043903
spz GeneProduct ensembl:FBgn0003495
GNBP2 GeneProduct ensembl:FBgn0040322
PIAS GeneProduct ncbigene:35927
PGRP-LE GeneProduct ensembl:FBgn0030695
GNBP1 GeneProduct ensembl:FBgn0040323
Relish GeneProduct uniprot:Q94527
Fadd GeneProduct ensembl:FBgn0038928
spz2 GeneProduct uniprot:Q8IRB0
Dredd GeneProduct ensembl:FBgn0020381
dome GeneProduct ensembl:FBgn0043903
GNBP3 GeneProduct ensembl:FBgn0040321
JAK GeneProduct uniprot:Q24592
JAK GeneProduct uniprot:Q24592
STAT GeneProduct uniprot:Q24151
STAT GeneProduct uniprot:Q24151
STAT GeneProduct uniprot:Q24151
STAT GeneProduct uniprot:Q24151
Relish GeneProduct uniprot:Q94527
Effete GeneProduct uniprot:P25867
Bendless GeneProduct uniprot:P35128
Uev1a GeneProduct uniprot:Q9VRL1
IAP2 GeneProduct ensembl:Q24307
upd2 GeneProduct ensembl:FBgn0030904
Protein Toll Protein uniprot:P08953
Cactus Protein uniprot:M9PD95
Protein Tube Protein uniprot:P22812
JNK Protein uniprot:P92208
Protein pellino Protein uniprot:O77237
Pelle Protein uniprot:Q05652
Dorsal Protein uniprot:C7LA93 Dorsal Not Specified
Dorsal Protein uniprot:C7LA93 Dorsal Not Specified


  1. The “ubiquitous” reality of vector immunology. Severo MS, Sakhon OS, Choy A, Stephens KD, Pedra JHF. Cell Microbiol. 2013 Jul;15(7):1070–8. PubMed Europe PMC Scholia