Entry Name Yersinia infection - Pteropus vampyrus (large flying fox)
Description Pathogenic Yersinia injects virulent Yersinia outer proteins (Yops) into the host cell through a type three secretion system (T3SS) to express its pathogenicity. Through inactivation of small GTPases by YopT protease, YopE GTPase-activating protein, and YpkA/YopO sequestration of GDP-bound small GTPases, Yersinia prevents its uptake by phagocytic cells and disrupts the actin cytoskeleton. YopH phosphatase shuts down phagocytosis by dephosphorylating key host proteins as well as suppresses T cell activation. Yersinia induces macrophage pyroptosis via YopB/YopD activation of canonical and noncanonical inflammasomes and YopT/YopE-mediated activation of pyrin. These effects are counteracted by YopK and YopM. YopP/J is a member of an ubiquitin-like protein cysteine protease family and simultaneously targets signaling components of the MAPK and NF-kappaB signaling pathways following activation of Toll-like receptor4 to inhibit production of proinflammatory cytokines.
Class Human Diseases; Infectious disease: bacterialBRITE hierarchy
Pathway map Disease Organism Pteropus vampyrus (large flying fox) [GN:
pvp ]
Gene 105289211 ARPC3; actin-related protein 2/3 complex subunit 3 isoform X1 [KO:K05756 ]
105289440 TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404 ]
105290433 CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393 ]
105290514 WASF2; wiskott-Aldrich syndrome protein family member 2 [KO:K05748 ]
105293029 NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580 ]
105294623 RAC1; LOW QUALITY PROTEIN: ras-related C3 botulinum toxin substrate 1 [KO:K04392 ]
105294862 ARPC5L; actin-related protein 2/3 complex subunit 5-like protein [KO:K05754 ]
105295639 MYD88; myeloid differentiation primary response protein MyD88 [KO:K04729 ]
105296040 NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332 ]
105296605 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
105298074 TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403 ]
105298188 ELMO2; engulfment and cell motility protein 2 isoform X1 [KO:K18985 ]
105299048 ARPC4; actin-related protein 2/3 complex subunit 4 isoform X2 [KO:K05755 ]
105299371 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X3 [KO:K02649 ]
105300484 ARHGEF28; rho guanine nucleotide exchange factor 28 isoform X1 [KO:K21072 ]
105301185 BAIAP2; brain-specific angiogenesis inhibitor 1-associated protein 2 [KO:K05627 ]
105301337 ARHGEF7; rho guanine nucleotide exchange factor 7 isoform X1 [KO:K13710 ]
105303020 NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446 ]
105304504 PYCARD; apoptosis-associated speck-like protein containing a CARD isoform X1 [KO:K12799 ]
105304587 LAT; linker for activation of T-cells family member 1 [KO:K07362 ]
105305354 BCAR1; breast cancer anti-estrogen resistance protein 1 isoform X4 [KO:K05726 ]
105305747 NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333 ]
105307215 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
105307342 ARHGEF1; rho guanine nucleotide exchange factor 1 isoform X1 [KO:K12330 ]
105307575 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
105308956 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X2 [KO:K00922 ] [EC:2.7.1.153 ]
105309343 NLRP3; NACHT, LRR and PYD domains-containing protein 3 [KO:K12800 ]
105309511 ARHGEF12; rho guanine nucleotide exchange factor 12 isoform X1 [KO:K07532 ]
105311532 RAC2; ras-related C3 botulinum toxin substrate 2 isoform X2 [KO:K07860 ]
Compound C01245 D-myo-Inositol 1,4,5-trisphosphate
C04637 1-Phosphatidyl-D-myo-inositol 4,5-bisphosphate
C05981 Phosphatidylinositol-3,4,5-trisphosphate
Reference Authors Pha K, Navarro L
Title Yersinia type III effectors perturb host innate immune responses.
Journal Reference Authors Pinaud L, Sansonetti PJ, Phalipon A
Title Host Cell Targeting by Enteropathogenic Bacteria T3SS Effectors.
Journal Reference Authors Huveneers S, Danen EH
Title Adhesion signaling - crosstalk between integrins, Src and Rho.
Journal Reference Authors Angot A, Vergunst A, Genin S, Peeters N
Title Exploitation of eukaryotic ubiquitin signaling pathways by effectors translocated by bacterial type III and type IV secretion systems.
Journal Reference Authors Bliska JB
Title Yop effectors of Yersinia spp. and actin rearrangements.
Journal Reference Authors Gustavsson A, Yuan M, Fallman M
Title Temporal dissection of beta1-integrin signaling indicates a role for p130Cas-Crk in filopodia formation.
Journal Reference Authors Bruce-Staskal PJ, Weidow CL, Gibson JJ, Bouton AH
Title Cas, Fak and Pyk2 function in diverse signaling cascades to promote Yersinia uptake.
Journal J Cell Sci 115:2689-700 (2002)
Reference Authors McGee K, Zettl M, Way M, Fallman M
Title A role for N-WASP in invasin-promoted internalisation.
Journal Reference Authors Pizarro-Cerda J, Cossart P
Title Subversion of phosphoinositide metabolism by intracellular bacterial pathogens.
Journal Reference Authors Chung LK, Park YH, Zheng Y, Brodsky IE, Hearing P, Kastner DL, Chae JJ, Bliska JB
Title The Yersinia Virulence Factor YopM Hijacks Host Kinases to Inhibit Type III Effector-Triggered Activation of the Pyrin Inflammasome.
Journal Reference Authors Schotte P, Denecker G, Van Den Broeke A, Vandenabeele P, Cornelis GR, Beyaert R
Title Targeting Rac1 by the Yersinia effector protein YopE inhibits caspase-1-mediated maturation and release of interleukin-1beta.
Journal Reference Authors Orth K, Palmer LE, Bao ZQ, Stewart S, Rudolph AE, Bliska JB, Dixon JE
Title Inhibition of the mitogen-activated protein kinase kinase superfamily by a Yersinia effector.
Journal Reference Authors Zhou H, Monack DM, Kayagaki N, Wertz I, Yin J, Wolf B, Dixit VM
Title Yersinia virulence factor YopJ acts as a deubiquitinase to inhibit NF-kappa B activation.
Journal Reference Authors Haase R, Richter K, Pfaffinger G, Courtois G, Ruckdeschel K
Title Yersinia outer protein P suppresses TGF-beta-activated kinase-1 activity to impair innate immune signaling in Yersinia enterocolitica-infected cells.
Journal Reference Authors Thiefes A, Wolf A, Doerrie A, Grassl GA, Matsumoto K, Autenrieth I, Bohn E, Sakurai H, Niedenthal R, Resch K, Kracht M
Title The Yersinia enterocolitica effector YopP inhibits host cell signalling by inactivating the protein kinase TAK1 in the IL-1 signalling pathway.
Journal Reference Authors Rosadini CV, Zanoni I, Odendall C, Green ER, Paczosa MK, Philip NH, Brodsky IE, Mecsas J, Kagan JC
Title A Single Bacterial Immune Evasion Strategy Dismantles Both MyD88 and TRIF Signaling Pathways Downstream of TLR4.
Journal Reference Authors Rolan HG, Durand EA, Mecsas J
Title Identifying Yersinia YopH-targeted signal transduction pathways that impair neutrophil responses during in vivo murine infection.
Journal Reference Authors Alonso A, Bottini N, Bruckner S, Rahmouni S, Williams S, Schoenberger SP, Mustelin T
Title Lck dephosphorylation at Tyr-394 and inhibition of T cell antigen receptor signaling by Yersinia phosphatase YopH.
Journal Related pvp04620 Toll-like receptor signaling pathway
pvp04621 NOD-like receptor signaling pathway
pvp04660 T cell receptor signaling pathway
pvp04666 Fc gamma R-mediated phagocytosis
pvp04810 Regulation of actin cytoskeleton
KO pathway
