ENTITY_REFERENCE_NOTES= pelle Uniprot: Q05652
ENTITY_REFERENCE_NOTES= embryonic polarity protein dorsal Uniprot: P15330
ENTITY_REFERENCE_NOTES= serpin 27A Uniprot: Q9V3N1
ENTITY_REFERENCE_NOTES= Slimb Uniprot: P44382
ENTITY_REFERENCE_NOTES= Protein spaetzle Uniprot: P48607
ENTITY_REFERENCE_NOTES= Uniprot: Q9VCJ8 Flybase: CG16705
ENTITY_REFERENCE_ID_DESC=Toll_pathway_drosophila.PROTEIN.GENERIC.SPZ_br_full length
ENTITY_REFERENCE_NOTES= MyD88 addaptor protein Uniprot: Q7K105
MODEL_NOTES= In Drosophila, the Toll pathway establishes the embryonic dorsoventral axis and triggers innate immune responses to infection, along with the Imd pathway. In response to Gram-positive bacterial and fungal pathogens, the Toll pathway is activated. Lysine-type peptidoglycans, present in many Gram-positive bacteria, interact with soluble receptors PGRP-SA and PGRP-SD and trigger a serine protease cascade which results in the enzymatic processing of the full-length Spatzle (SPZ) dimer ligand. The final serine protease in the cascade is believed to be Easter (EA) in dorsoventral formation and Spatzle-processing enzyme aka SPE (CG16705) in an innate immunity response. The processed SPZ dimer binds to the extracellular part of the Toll (TL) receptor at the plasma membrane. This causes TL to activate and dimerise through its cytoplasmic domains. In response to this activity, the adaptor proteins MYD88, Tube (TUB), and the Ser/Thr kinase Pelle (PLL) are recruited to the TL receptor cytoplasmic region to form the ‘signalling complex’. PLL is activated, autophosphorylates and then dissociates from the ‘signalling complex’. The next stage is unclear but it is believed that PLL and an unknown kinase tentatively labelled the ‘Cactus kinase’ phosphorylate NF-kappaB inhibitor orthologue, Cactus (CACT). CACT is complexed to NF-kappaB orthologue dimers of either Dorsal (DL) in dorsoventral polarity or Dorsal-related immunity factor, Dif (DIF) in the innate immunity response. The phosphorylated CACT is ubiquitinated and degraded by the 26S proteasome, releasing the free DL/DIF dimer. This translocates to the nucleus where it activates transcription of genes encoding a battery of antimicrobial peptides in the immune response or genes that organise dorsoventral patterning.
ENTITY_REFERENCE_NOTES= serine protease easter Uniprot: P13582 Uniprot: Q9VCJ8? (CG16705, SPE)