Entry Name Yersinia infection
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 Ortholog table Disease Orthology K07863 Ras homolog gene family, member G
K04438 C-crk adapter molecule crk
K05726 breast cancer anti-estrogen resistance 1
K12366 engulfment and cell motility protein 1
K18985 engulfment and cell motility protein 2
K13708 dedicator of cytokinesis protein 1
K06856 immunoglobulin heavy chain
K06472 low affinity immunoglobulin gamma Fc receptor II-a
K04392 Ras-related C3 botulinum toxin substrate 1
K07860 Ras-related C3 botulinum toxin substrate 2
K07861 Ras-related C3 botulinum toxin substrate 3
K07941 ADP-ribosylation factor 6
K23612 neural Wiskott-Aldrich syndrome protein
K17260 actin-related protein 2
K18584 actin-related protein 3
K05757 actin related protein 2/3 complex, subunit 1A/1B
K05758 actin related protein 2/3 complex, subunit 2
K05756 actin related protein 2/3 complex, subunit 3
K05755 actin related protein 2/3 complex, subunit 4
K05754 actin related protein 2/3 complex, subunit 5
K19475 WAS/WASL-interacting protein
K05627 BAI1-associated protein 2
K05748 WAS protein family, member 2
K12487 G protein-coupled receptor kinase interactor 2
K13710 Rho guanine nucleotide exchange factor 7
K04393 cell division control protein 42
K05747 Wiskott-Aldrich syndrome protein
K04634 guanine nucleotide-binding protein G(q) subunit alpha
K07532 Rho guanine nucleotide exchange factor 12
K12330 Rho guanine nucleotide exchange factor 1
K21072 A-kinase anchor protein 28
K04513 Ras homolog gene family, member A
K23471 src kinase-associated phosphoprotein 2
K08599 YopT peptidase [EC:3.4.22.-]
K23473 outer membrane virulence protein YopE
K12800 NACHT, LRR and PYD domains-containing protein 3
K12805 NLR family CARD domain-containing protein 4
K12799 apoptosis-associated speck-like protein containing a CARD
K23478 outer membrane protein YopM
K04729 myeloid differentiation primary response protein MyD88
K07210 inhibitor of nuclear factor kappa-B kinase subunit gamma
K04467 inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10 ]
K07209 inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10 ]
K04734 NF-kappa-B inhibitor alpha
K02580 nuclear factor NF-kappa-B p105 subunit
K04735 transcription factor p65
K04440 mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24 ]
K04379 proto-oncogene protein c-fos
K04448 transcription factor AP-1
K05842 toll-like receptor adapter molecule 1
K05411 interferon regulatory factor 3
K03156 tumor necrosis factor superfamily, member 2
K00922 phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153 ]
K02649 phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K06454 T-cell surface glycoprotein CD4
K06458 T-cell surface glycoprotein CD8 alpha chain
K06459 T-cell surface glycoprotein CD8 beta chain
K10784 T cell receptor alpha chain V region
K10785 T-cell receptor beta chain V region
K07362 linker for activation of T cells family member 1
K07361 lymphocyte cytosolic protein 2
K05730 guanine nucleotide exchange factor VAV
K04446 nuclear factor of activated T-cells, cytoplasmic 1
K17332 nuclear factor of activated T-cells, cytoplasmic 2
K17333 nuclear factor of activated T-cells, cytoplasmic 3
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 ko04620 Toll-like receptor signaling pathway
ko04621 NOD-like receptor signaling pathway
ko04660 T cell receptor signaling pathway
ko04666 Fc gamma R-mediated phagocytosis
ko04810 Regulation of actin cytoskeleton
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