Entry Name Yersinia infection - Ursus arctos (brown bear)
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 Ursus arctos (brown bear) [GN:
uah ]
Gene 113241761 TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X1 [KO:K04403 ]
113243505 ARHGEF1; rho guanine nucleotide exchange factor 1 isoform X3 [KO:K12330 ]
113244528 BAIAP2; brain-specific angiogenesis inhibitor 1-associated protein 2 isoform X1 [KO:K05627 ]
113244670 RAC3; ras-related C3 botulinum toxin substrate 3 isoform X1 [KO:K07861 ]
113244955 VAV3; guanine nucleotide exchange factor VAV3 isoform X1 [KO:K05730 ]
113247462 NLRP3; NACHT, LRR and PYD domains-containing protein 3 isoform X1 [KO:K12800 ]
113248529 ARHGEF7; rho guanine nucleotide exchange factor 7 isoform X3 [KO:K13710 ]
113252399 NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333 ]
113252495 BCAR1; breast cancer anti-estrogen resistance protein 1 isoform X2 [KO:K05726 ]
113253544 NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446 ]
113253781 MYD88; myeloid differentiation primary response protein MyD88 isoform X1 [KO:K04729 ]
113253989 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
113254730 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X2 [KO:K02649 ]
113254799 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
113255216 ARHGEF28; rho guanine nucleotide exchange factor 28 isoform X9 [KO:K21072 ]
113255266 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
113256705 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
113257149 ARPC4; actin-related protein 2/3 complex subunit 4 isoform X1 [KO:K05755 ]
113258609 PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116 ] [EC:3.1.4.11 ]
113258677 ELMO2; engulfment and cell motility protein 2 isoform X1 [KO:K18985 ]
113258729 NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332 ]
113259542 TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404 ]
113259947 ARHGEF12; rho guanine nucleotide exchange factor 12 isoform X1 [KO:K07532 ]
113261826 SKAP2; src kinase-associated phosphoprotein 2 isoform X2 [KO:K23471 ]
113262254 WIPF3; WAS/WASL-interacting protein family member 3 isoform X3 [KO:K19475 ]
113262738 ARPC5; actin-related protein 2/3 complex subunit 5 isoform X2 [KO:K05754 ]
113262812 ELMO1; engulfment and cell motility protein 1 isoform X1 [KO:K12366 ]
113263101 NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X3 [KO:K02580 ]
113263592 WASL; actin nucleation-promoting factor WASL isoform X1 [KO:K23612 ]
113266404 ARPC5L; actin-related protein 2/3 complex subunit 5-like protein [KO:K05754 ]
113266577 VAV2; guanine nucleotide exchange factor VAV2 isoform X1 [KO:K05730 ]
113266963 ARPC3; actin-related protein 2/3 complex subunit 3 isoform X1 [KO:K05756 ]
113267622 LAT; linker for activation of T-cells family member 1 isoform X1 [KO:K07362 ]
113267943 RAC1; ras-related C3 botulinum toxin substrate 1 isoform X2 [KO:K04392 ]
113269831 GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634 ]
113270537 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
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 uah04620 Toll-like receptor signaling pathway
uah04621 NOD-like receptor signaling pathway
uah04660 T cell receptor signaling pathway
uah04666 Fc gamma R-mediated phagocytosis
uah04810 Regulation of actin cytoskeleton
KO pathway
