KEGG   PATHWAY: ptg05135
Entry
ptg05135                    Pathway                                
Name
Yersinia infection - Panthera tigris altaica (Amur tiger)
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
ptg05135  Yersinia infection
ptg05135

Organism
Panthera tigris altaica (Amur tiger) [GN:ptg]
Gene
102970250  FN1; fibronectin 1 [KO:K05717]
102966166  ITGA4; integrin subunit alpha 4 [KO:K06483]
102959936  ITGA5; integrin subunit alpha 5 [KO:K06484]
102967350  ITGB1; integrin subunit beta 1 [KO:K05719]
102954676  RHOG; ras homolog family member G [KO:K07863]
102965418  rho-related GTP-binding protein RhoG-like [KO:K07863]
102968822  SRC; SRC proto-oncogene, non-receptor tyrosine kinase [KO:K05704] [EC:2.7.10.2]
102953254  PTK2; protein tyrosine kinase 2 [KO:K05725] [EC:2.7.10.2]
102955963  PTK2B; protein tyrosine kinase 2 beta [KO:K05871] [EC:2.7.10.2]
102957241  CRKL; CRK like proto-oncogene, adaptor protein [KO:K04438]
102956621  CRK; CRK proto-oncogene, adaptor protein [KO:K04438]
102961947  BCAR1; BCAR1, Cas family scaffolding protein [KO:K05726]
102961652  ELMO1; engulfment and cell motility 1 [KO:K12366]
102962506  ELMO2; engulfment and cell motility 2 [KO:K18985]
102973006  DOCK1; dedicator of cytokinesis 1 [KO:K13708]
102968561  RAC1; ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) [KO:K04392]
102961922  RAC2; ras-related C3 botulinum toxin substrate 2 (rho family, small GTP binding protein Rac2) [KO:K07860]
102955504  RAC3; ras-related C3 botulinum toxin substrate 3 (rho family, small GTP binding protein Rac3) [KO:K07861]
102958782  PIP5K1C; phosphatidylinositol-4-phosphate 5-kinase type 1 gamma [KO:K00889] [EC:2.7.1.68]
102966331  PIP5K1B; phosphatidylinositol-4-phosphate 5-kinase type 1 beta [KO:K00889] [EC:2.7.1.68]
102952372  PIP5K1A; phosphatidylinositol-4-phosphate 5-kinase type 1 alpha [KO:K00889] [EC:2.7.1.68]
102959274  ARF6; ADP ribosylation factor 6 [KO:K07941]
102972678  WASL; Wiskott-Aldrich syndrome like [KO:K23612]
102971744  ACTR2; ARP2 actin related protein 2 homolog [KO:K17260]
102965409  ACTR3B; ARP3 actin related protein 3 homolog B [KO:K18584]
102965872  ACTR3; ARP3 actin related protein 3 homolog [KO:K18584]
102963554  ARPC1B; actin related protein 2/3 complex subunit 1B [KO:K05757]
102963836  ARPC1A; actin related protein 2/3 complex subunit 1A [KO:K05757]
102952821  ARPC2; actin related protein 2/3 complex subunit 2 [KO:K05758]
102951259  ARPC3; actin related protein 2/3 complex subunit 3 [KO:K05756]
102956425  ARPC4; actin related protein 2/3 complex subunit 4 [KO:K05755]
102953170  ARPC5L; actin related protein 2/3 complex subunit 5 like [KO:K05754]
102968345  ARPC5; actin related protein 2/3 complex subunit 5 [KO:K05754]
102971629  ACTG1; actin gamma 1 [KO:K05692]
102971401  ACTB; actin beta [KO:K05692]
102956710  WIPF1; WAS/WASL interacting protein family member 1 [KO:K19475]
102967988  WIPF2; WAS/WASL interacting protein family member 2 [KO:K19475]
102949036  WIPF3; WAS/WASL interacting protein family member 3 [KO:K19475]
102959420  BAIAP2; BAI1 associated protein 2 [KO:K05627]
102954999  WASF2; WAS protein family member 2 [KO:K05748]
102953161  PXN; paxillin [KO:K05760]
102971051  GIT2; GIT ArfGAP 2 [KO:K12487]
102952488  ARHGEF7; Rho guanine nucleotide exchange factor 7 [KO:K13710]
102973021  CDC42; cell division cycle 42 [KO:K04393]
102951203  WAS; Wiskott-Aldrich syndrome [KO:K05747]
102954227  GNAQ; G protein subunit alpha q [KO:K04634]
102949630  ARHGEF12; Rho guanine nucleotide exchange factor 12 [KO:K07532]
102956204  ARHGEF1; Rho guanine nucleotide exchange factor 1 [KO:K12330]
102966346  ARHGEF28; Rho guanine nucleotide exchange factor 28 [KO:K21072]
102952555  RHOA; ras homolog family member A [KO:K04513]
102963520  ROCK1; Rho associated coiled-coil containing protein kinase 1 [KO:K04514] [EC:2.7.11.1]
102949986  ROCK2; Rho associated coiled-coil containing protein kinase 2 [KO:K17388] [EC:2.7.11.1]
102958889  FYB; FYN binding protein [KO:K17698]
102952418  SKAP2; src kinase associated phosphoprotein 2 [KO:K23471]
102954761  NACHT, LRR and PYD domains-containing protein 3-like [KO:K12800]
102958929  NLRC4; NLR family CARD domain containing 4 [KO:K12805]
102960418  PKN1; protein kinase N1 [KO:K06071] [EC:2.7.11.13]
102961482  PKN2; protein kinase N2 [KO:K23691] [EC:2.7.11.13]
102959548  RPS6KA1; ribosomal protein S6 kinase A1 [KO:K04373] [EC:2.7.11.1]
102964555  RPS6KA3; ribosomal protein S6 kinase A3 [KO:K04373] [EC:2.7.11.1]
102954716  RPS6KA2; ribosomal protein S6 kinase A2 [KO:K04373] [EC:2.7.11.1]
102959403  RPS6KA6; ribosomal protein S6 kinase A6 [KO:K04373] [EC:2.7.11.1]
102952100  MEFV; MEFV, pyrin innate immunity regulator [KO:K12803]
102966775  LIMK1; LIM domain kinase 1 [KO:K05743] [EC:2.7.11.1]
102965910  PYCARD; apoptosis-associated speck-like protein containing a CARD [KO:K12799]
102952004  IL18; interleukin 18 [KO:K05482]
102951272  IL1B; interleukin 1 beta [KO:K04519]
102959529  TLR4; toll like receptor 4 [KO:K10160]
102952059  MYD88; myeloid differentiation primary response 88 [KO:K04729]
102962570  IRAK4; interleukin 1 receptor associated kinase 4 [KO:K04733] [EC:2.7.11.1]
102960157  TRAF6; TNF receptor associated factor 6 [KO:K03175] [EC:2.3.2.27]
102966802  TRAF2; TNF receptor associated factor 2 [KO:K03173] [EC:2.3.2.27]
102950874  TAB1; TGF-beta activated kinase 1 (MAP3K7) binding protein 1 [KO:K04403]
102959790  TAB2; TGF-beta activated kinase 1/MAP3K7 binding protein 2 [KO:K04404]
102963341  MAP3K7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
102949289  CHUK; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
102963734  IKBKB; inhibitor of nuclear factor kappa B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
102956127  NFKBIA; NFKB inhibitor alpha [KO:K04734]
102964232  NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
102951132  RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
102969757  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
102956808  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102964841  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102960964  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102949954  MAP2K3; mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
102966485  MAP2K6; mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
102968191  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
102960306  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
102960590  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
102968482  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
102966812  MAP2K4; mitogen-activated protein kinase kinase 4 [KO:K04430] [EC:2.7.12.2]
102949140  MAP2K7; mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
102959159  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
102950880  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
102963096  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
102952769  FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379]
102958666  JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
102951327  TICAM1; toll like receptor adaptor molecule 1 [KO:K05842]
102960158  TBK1; TANK binding kinase 1 [KO:K05410] [EC:2.7.11.10]
102956602  IRF3; interferon regulatory factor 3 [KO:K05411]
102958919  TNF; tumor necrosis factor [KO:K03156]
102968780  IL6; interleukin 6 [KO:K05405]
102953898  interleukin-8-like [KO:K10030]
102953024  IL8; interleukin-8 [KO:K10030]
102960421  IFNB1; interferon beta 1 [KO:K05415]
102953082  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
102965070  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
102972487  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
102949853  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
102952993  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
102967709  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
102952603  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
102954757  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
102961382  GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
102967278  CCL2; C-C motif chemokine 2 [KO:K14624]
102954103  CD4; CD4 molecule [KO:K06454]
102963003  CD8A; CD8a molecule [KO:K06458]
102963282  CD8B; CD8b molecule [KO:K06459]
102967826  LCK; LCK proto-oncogene, Src family tyrosine kinase [KO:K05856] [EC:2.7.10.2]
102969244  ZAP70; tyrosine-protein kinase ZAP-70 [KO:K07360] [EC:2.7.10.2]
102972473  LAT; linker for activation of T-cells [KO:K07362]
102948687  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
102967454  VAV1; vav guanine nucleotide exchange factor 1 [KO:K05730]
102959251  VAV2; vav guanine nucleotide exchange factor 2 [KO:K05730]
102955544  VAV3; vav guanine nucleotide exchange factor 3 [KO:K05730]
102952137  PLCG1; phospholipase C gamma 1 [KO:K01116] [EC:3.1.4.11]
102969678  NFATC2; nuclear factor of activated T-cells 2 [KO:K17332]
102972106  NFATC3; nuclear factor of activated T-cells 3 [KO:K17333]
102957506  IL2; interleukin 2 [KO:K05429]
102957558  IL10; interleukin 10 [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
  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
  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
  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
  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
  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
  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
  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
FEBS Lett 509:59-65 (2001)
DOI:10.1016/S0014-5793(01)03139-8
Reference
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
ptg04510  Focal adhesion
ptg04620  Toll-like receptor signaling pathway
ptg04621  NOD-like receptor signaling pathway
ptg04660  T cell receptor signaling pathway
ptg04666  Fc gamma R-mediated phagocytosis
ptg04810  Regulation of actin cytoskeleton
KO pathway
ko05135   
LinkDB

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