Entry
Name
Yersinia infection - Enhydra lutris kenyoni (northern sea otter)
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: bacterial
BRITE hierarchy
Pathway map
Ortholog table
Organism
Enhydra lutris kenyoni (northern sea otter) [GN:
elk ]
Gene
111152853 breast cancer anti-estrogen resistance protein 1 isoform X1 [KO:K05726 ]
111145636 ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392 ]
111160304 ras-related C3 botulinum toxin substrate 3 isoform X1 [KO:K07861 ]
111145545 actin-related protein 2/3 complex subunit 1A isoform X1 [KO:K05757 ]
111144070 actin-related protein 2/3 complex subunit 2 isoform X1 [KO:K05758 ]
111156780 LOW QUALITY PROTEIN: actin-related protein 2/3 complex subunit 3-like [KO:K05756 ]
111143772 actin-related protein 2/3 complex subunit 4 isoform X1 [KO:K05755 ]
111150789 actin-related protein 2/3 complex subunit 5 isoform X1 [KO:K05754 ]
111146006 actin-related protein 2/3 complex subunit 5-like protein isoform X1 [KO:K05754 ]
111160439 brain-specific angiogenesis inhibitor 1-associated protein 2 isoform X1 [KO:K05627 ]
111153498 guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634 ]
111139817 NACHT, LRR and PYD domains-containing protein 3 isoform X1 [KO:K12800 ]
111162289 apoptosis-associated speck-like protein containing a CARD isoform X1 [KO:K12799 ]
111159049 myeloid differentiation primary response protein MyD88 [KO:K04729 ]
111157505 TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403 ]
111147521 TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404 ]
111155003 LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922 ] [EC:2.7.1.153 ]
111154641 phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
111143470 phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649 ]
111155224 phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
111143790 phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
111162219 linker for activation of T-cells family member 1 isoform X1 [KO:K07362 ]
111154209 nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446 ]
111141582 LOW QUALITY PROTEIN: nuclear factor of activated T-cells, cytoplasmic 2 [KO:K17332 ]
111152752 nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333 ]
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 pathway
elk04620 Toll-like receptor signaling pathway
elk04621 NOD-like receptor signaling pathway
elk04660 T cell receptor signaling pathway
elk04666 Fc gamma R-mediated phagocytosis
elk04810 Regulation of actin cytoskeleton
KO pathway
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