KEGG   PATHWAY: ptr05135
Entry
ptr05135                    Pathway                                
Name
Yersinia infection - Pan troglodytes (chimpanzee)
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
Pathway map
ptr05135  Yersinia infection
ptr05135

Organism
Pan troglodytes (chimpanzee) [GN:ptr]
Gene
459926  FN1; fibronectin isoform X18 [KO:K05717]
470596  ITGA4; integrin alpha-4 isoform X1 [KO:K06483]
451958  ITGA5; integrin alpha-5 isoform X1 [KO:K06484]
450396  ITGB1; integrin beta-1 isoform X1 [KO:K05719]
748092  RHOG; rho-related GTP-binding protein RhoG [KO:K07863]
458229  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
464422  PTK2; focal adhesion kinase 1 isoform X15 [KO:K05725] [EC:2.7.10.2]
464073  PTK2B; protein-tyrosine kinase 2-beta isoform X1 [KO:K05871] [EC:2.7.10.2]
747142  CRK; adapter molecule crk isoform X1 [KO:K04438]
107970369  CRKL; crk-like protein [KO:K04438]
454246  BCAR1; breast cancer anti-estrogen resistance protein 1 isoform X1 [KO:K05726]
463354  ELMO1; engulfment and cell motility protein 1 isoform X2 [KO:K12366]
458299  ELMO2; engulfment and cell motility protein 2 isoform X1 [KO:K18985]
104001055  DOCK1; dedicator of cytokinesis protein 1 isoform X1 [KO:K13708]
100608894  immunoglobulin heavy variable 3-23 [KO:K06856]
104002202  putative V-set and immunoglobulin domain-containing-like protein IGHV4OR15-8 [KO:K06856]
104002200  immunoglobulin heavy variable 6-1 [KO:K06856]
450194  FCGR2A; low affinity immunoglobulin gamma Fc region receptor II-a precursor [KO:K06472]
741907  RAC1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
742575  RAC2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]
747131  RAC3; ras-related C3 botulinum toxin substrate 3 isoform X1 [KO:K07861]
455590  PIP5K1C; phosphatidylinositol 4-phosphate 5-kinase type-1 gamma isoform X1 [KO:K00889] [EC:2.7.1.68]
464513  PIP5K1B; phosphatidylinositol 4-phosphate 5-kinase type-1 beta isoform X1 [KO:K00889] [EC:2.7.1.68]
457288  PIP5K1A; phosphatidylinositol 4-phosphate 5-kinase type-1 alpha [KO:K00889] [EC:2.7.1.68]
452892  ARF6; ADP-ribosylation factor 6 [KO:K07941]
463688  WASL; neural Wiskott-Aldrich syndrome protein [KO:K23612]
746973  ACTR2; actin-related protein 2 isoform X1 [KO:K17260]
736054  ACTR3C; actin-related protein 3C isoform X1 [KO:K18584]
738748  ACTR3B; LOW QUALITY PROTEIN: actin-related protein 3B [KO:K18584]
459563  ACTR3; actin-related protein 3 [KO:K18584]
463568  ARPC1B; actin-related protein 2/3 complex subunit 1B [KO:K05757]
737235  ARPC1A; actin-related protein 2/3 complex subunit 1A [KO:K05757]
459938  ARPC2; actin-related protein 2/3 complex subunit 2 [KO:K05758]
737048  ARPC3; actin-related protein 2/3 complex subunit 3 [KO:K05756]
100614809  ARPC4; actin-related protein 2/3 complex subunit 4 isoform X4 [KO:K05755]
464728  ARPC5L; actin-related protein 2/3 complex subunit 5-like protein [KO:K05754]
457574  ARPC5; actin-related protein 2/3 complex subunit 5 [KO:K05754]
746570  ACTG1; actin, cytoplasmic 2 [KO:K05692]
450133  ACTB; actin, cytoplasmic 1 [KO:K05692]
459755  WIPF1; WAS/WASL-interacting protein family member 1 [KO:K19475]
455039  WIPF2; WAS/WASL-interacting protein family member 2 [KO:K19475]
463322  WIPF3; WAS/WASL-interacting protein family member 3 [KO:K19475]
454951  BAIAP2; brain-specific angiogenesis inhibitor 1-associated protein 2 isoform X3 [KO:K05627]
456675  WASF2; wiskott-Aldrich syndrome protein family member 2 [KO:K05748]
473870  wiskott-Aldrich syndrome protein family member 2-like [KO:K05748]
452303  PXN; paxillin isoform X11 [KO:K05760]
452227  GIT2; ARF GTPase-activating protein GIT2 isoform X1 [KO:K12487]
452673  ARHGEF7; rho guanine nucleotide exchange factor 7 isoform X17 [KO:K13710]
456609  CDC42; cell division control protein 42 homolog [KO:K04393]
743187  WAS; wiskott-Aldrich syndrome protein [KO:K05747]
472962  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634]
451618  ARHGEF12; rho guanine nucleotide exchange factor 12 isoform X1 [KO:K07532]
456067  ARHGEF1; rho guanine nucleotide exchange factor 1 isoform X1 [KO:K12330]
461808  ARHGEF28; rho guanine nucleotide exchange factor 28 isoform X1 [KO:K21072]
461014  RHOA; transforming protein RhoA [KO:K04513]
455326  ROCK1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.1]
470307  ROCK2; rho-associated protein kinase 2 isoform X1 [KO:K17388] [EC:2.7.11.1]
461906  FYB1; FYN-binding protein 1 isoform X1 [KO:K17698]
463306  SKAP2; src kinase-associated phosphoprotein 2 isoform X1 [KO:K23471]
469743  NLRP3; NACHT, LRR and PYD domains-containing protein 3 isoform X1 [KO:K12800]
459135  NLRC4; NLR family CARD domain-containing protein 4 [KO:K12805]
455785  PKN1; serine/threonine-protein kinase N1 isoform X1 [KO:K06071] [EC:2.7.11.13]
456998  PKN2; serine/threonine-protein kinase N2 isoform X1 [KO:K23691] [EC:2.7.11.13]
450110  RPS6KA3; ribosomal protein S6 kinase alpha-3 isoform X1 [KO:K04373] [EC:2.7.11.1]
456664  RPS6KA1; ribosomal protein S6 kinase alpha-1 isoform X5 [KO:K04373] [EC:2.7.11.1]
463127  RPS6KA2; ribosomal protein S6 kinase alpha-2 isoform X1 [KO:K04373] [EC:2.7.11.1]
743327  RPS6KA6; ribosomal protein S6 kinase alpha-6 isoform X1 [KO:K04373] [EC:2.7.11.1]
107968776  MEFV; pyrin isoform X1 [KO:K12803]
463466  LIMK1; LIM domain kinase 1 isoform X1 [KO:K05743] [EC:2.7.11.1]
742444  PYCARD; apoptosis-associated speck-like protein containing a CARD isoform X2 [KO:K12799]
101058924  CASP1; caspase-1 isoform X4 [KO:K01370] [EC:3.4.22.36]
739011  IL18; interleukin-18 isoform X1 [KO:K05482]
450200  IL1B; interleukin-1 beta [KO:K04519]
743242  TLR4; toll-like receptor 4 precursor [KO:K10160]
460269  MYD88; myeloid differentiation primary response protein MyD88 [KO:K04729]
466962  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X3 [KO:K04733] [EC:2.7.11.1]
451702  TRAF6; TNF receptor-associated factor 6 isoform X1 [KO:K03175] [EC:2.3.2.27]
464876  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
458845  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X1 [KO:K04403]
463057  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404]
462888  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
100610002  NF-kappa-B essential modulator [KO:K07210]
100609537  IKBKG; LOW QUALITY PROTEIN: NF-kappa-B essential modulator [KO:K07210]
450673  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
472749  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
467426  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
461406  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X3 [KO:K02580]
466665  RELA; transcription factor p65 [KO:K04735]
450188  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
456390  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
454037  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
458680  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
107972404  dual specificity mitogen-activated protein kinase kinase 3 isoform X1 [KO:K04432] [EC:2.7.12.2]
112206088  dual specificity mitogen-activated protein kinase kinase 3-like [KO:K04432] [EC:2.7.12.2]
468310  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X2 [KO:K04433] [EC:2.7.12.2]
450161  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
462644  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
747077  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
104003820  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
455065  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
743199  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X3 [KO:K04431] [EC:2.7.12.2]
450445  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
461358  MAPK10; mitogen-activated protein kinase 10 isoform X3 [KO:K04440] [EC:2.7.11.24]
462336  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
453047  FOS; proto-oncogene c-Fos [KO:K04379]
456893  JUN; transcription factor AP-1 [KO:K04448]
468677  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
452047  TBK1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
747565  IRF3; interferon regulatory factor 3 isoform X1 [KO:K05411]
494186  TNF; tumor necrosis factor [KO:K03156]
463288  IL6; interleukin-6 isoform X1 [KO:K05405]
471205  CXCL8; interleukin-8 [KO:K10030]
473183  IFNB1; interferon beta [KO:K05415]
460858  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
457922  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
471079  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
456565  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X2 [KO:K02649]
461836  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]
455855  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
456035  AKT2; RAC-beta serine/threonine-protein kinase isoform X4 [KO:K04456] [EC:2.7.11.1]
740898  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100609583  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100616510  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
748205  CCL2; C-C motif chemokine 2 [KO:K14624]
450124  CD4; T-cell surface glycoprotein CD4 precursor [KO:K06454]
735755  CD8A; T-cell surface glycoprotein CD8 alpha chain isoform X2 [KO:K06458]
470426  CD8B; T-cell surface glycoprotein CD8 beta chain isoform X4 [KO:K06459]
456715  LCK; tyrosine-protein kinase Lck isoform X1 [KO:K05856] [EC:2.7.10.2]
743494  T-cell receptor alpha chain V region RL-5 [KO:K10784]
100615597  BV7-9; T-cell receptor beta chain V region CTL-L17 [KO:K10785]
100613861  BV10-1; T-cell receptor beta chain V region C5 [KO:K10785]
472538  BV2; T-cell receptor beta chain V region CTL-L17 isoform X2 [KO:K10785]
743326  BV7-2; T-cell receptor beta chain V region CTL-L17 [KO:K10785]
100615500  BV7-8; T-cell receptor beta chain V region CTL-L17 [KO:K10785]
101058202  BV25-1; T-cell receptor beta chain V region PHDS203 [KO:K10785]
101057236  BV5-1; T-cell receptor beta chain V region CTL-L17 [KO:K10785]
104007424  uncharacterized protein LOC104007424 [KO:K10785]
100614611  uncharacterized protein LOC100614611 [KO:K10785]
472543  BV6-3; T-cell receptor beta chain V region CTL-L17 [KO:K10785]
459427  ZAP70; tyrosine-protein kinase ZAP-70 isoform X2 [KO:K07360] [EC:2.7.10.2]
743295  LAT; linker for activation of T-cells family member 1 isoform X5 [KO:K07362]
471734  LCP2; lymphocyte cytosolic protein 2 isoform X1 [KO:K07361]
455647  VAV1; proto-oncogene vav isoform X1 [KO:K05730]
473114  VAV2; guanine nucleotide exchange factor VAV2 isoform X1 [KO:K05730]
457076  VAV3; guanine nucleotide exchange factor VAV3 isoform X1 [KO:K05730]
458253  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
455485  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X2 [KO:K04446]
469972  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X2 [KO:K17332]
454184  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X6 [KO:K17333]
461472  IL2; interleukin-2 [KO:K05429]
469657  IL10; interleukin-10 precursor [KO:K05443]
Compound
C00076  Calcium cation
C00338  Lipopolysaccharide
C01245  D-myo-Inositol 1,4,5-trisphosphate
C04637  1-Phosphatidyl-D-myo-inositol 4,5-bisphosphate
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Reference
PMID:26981193
  Authors
Pha K, Navarro L
  Title
Yersinia type III effectors perturb host innate immune responses.
  Journal
World J Biol Chem 7:1-13 (2016)
DOI:10.4331/wjbc.v7.i1.1
Reference
PMID:29477730
  Authors
Pinaud L, Sansonetti PJ, Phalipon A
  Title
Host Cell Targeting by Enteropathogenic Bacteria T3SS Effectors.
  Journal
Trends Microbiol 26:266-283 (2018)
DOI:10.1016/j.tim.2018.01.010
Reference
PMID:19339545
  Authors
Huveneers S, Danen EH
  Title
Adhesion signaling - crosstalk between integrins, Src and Rho.
  Journal
J Cell Sci 122:1059-69 (2009)
DOI:10.1242/jcs.039446
Reference
PMID:17257058
  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
PLoS Pathog 3:e3 (2007)
DOI:10.1371/journal.ppat.0030003
Reference
PMID:10785635
  Authors
Bliska JB
  Title
Yop effectors of Yersinia spp. and actin rearrangements.
  Journal
Trends Microbiol 8:205-8 (2000)
DOI:10.1016/S0966-842X(00)01738-8
Reference
PMID:15044442
  Authors
Gustavsson A, Yuan M, Fallman M
  Title
Temporal dissection of beta1-integrin signaling indicates a role for p130Cas-Crk in filopodia formation.
  Journal
J Biol Chem 279:22893-901 (2004)
DOI:10.1074/jbc.M309693200
Reference
PMID:12077360
  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
PMID:11734206
  Authors
McGee K, Zettl M, Way M, Fallman M
  Title
A role for N-WASP in invasin-promoted internalisation.
  Journal
FEBS Lett 509:59-65 (2001)
DOI:10.1016/S0014-5793(01)03139-8
Reference
PMID:15516995
  Authors
Pizarro-Cerda J, Cossart P
  Title
Subversion of phosphoinositide metabolism by intracellular bacterial pathogens.
  Journal
Nat Cell Biol 6:1026-33 (2004)
DOI:10.1038/ncb1104-1026
Reference
PMID:27569559
  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
Cell Host Microbe 20:296-306 (2016)
DOI:10.1016/j.chom.2016.07.018
Reference
PMID:15060067
  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
J Biol Chem 279:25134-42 (2004)
DOI:10.1074/jbc.M401245200
Reference
PMID:10489373
  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
Science 285:1920-3 (1999)
DOI:10.1126/science.285.5435.1920
Reference
PMID:16301742
  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
J Exp Med 202:1327-32 (2005)
DOI:10.1084/jem.20051194
Reference
PMID:16339560
  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
J Immunol 175:8209-17 (2005)
DOI:10.4049/jimmunol.175.12.8209
Reference
PMID:16845370
  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
EMBO Rep 7:838-44 (2006)
DOI:10.1038/sj.embor.7400754
Reference
PMID:26651944
  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
Cell Host Microbe 18:682-93 (2015)
DOI:10.1016/j.chom.2015.11.006
Reference
PMID:24034616
  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
Cell Host Microbe 14:306-17 (2013)
DOI:10.1016/j.chom.2013.08.013
Reference
PMID:14623872
  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
J Biol Chem 279:4922-8 (2004)
DOI:10.1074/jbc.M308978200
Related
pathway
ptr04510  Focal adhesion
ptr04620  Toll-like receptor signaling pathway
ptr04621  NOD-like receptor signaling pathway
ptr04660  T cell receptor signaling pathway
ptr04666  Fc gamma R-mediated phagocytosis
ptr04810  Regulation of actin cytoskeleton
KO pathway
ko05135   
LinkDB

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