KEGG   PATHWAY: hai05135
Entry
hai05135                    Pathway                                
Name
Yersinia infection - Hipposideros armiger (great roundleaf bat)
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
hai05135  Yersinia infection
hai05135

Organism
Hipposideros armiger (great roundleaf bat) [GN:hai]
Gene
109380590  FN1; fibronectin isoform X1 [KO:K05717]
109392600  ITGA4; integrin alpha-4 [KO:K06483]
109391860  ITGA5; integrin alpha-5 [KO:K06484]
109388160  ITGB1; integrin beta-1 isoform X1 [KO:K05719]
109385596  rho-related GTP-binding protein RhoG-like [KO:K07863]
109372429  RHOG; rho-related GTP-binding protein RhoG isoform X1 [KO:K07863]
109384552  rho-related GTP-binding protein RhoG-like [KO:K07863]
109377191  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
109390857  PTK2; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
109379535  PTK2B; protein-tyrosine kinase 2-beta isoform X1 [KO:K05871] [EC:2.7.10.2]
109386906  CRK; adapter molecule crk isoform X1 [KO:K04438]
109376239  CRKL; crk-like protein [KO:K04438]
109384807  BCAR1; breast cancer anti-estrogen resistance protein 1 isoform X1 [KO:K05726]
109389817  ELMO1; engulfment and cell motility protein 1 isoform X1 [KO:K12366]
109379935  ELMO2; engulfment and cell motility protein 2 isoform X1 [KO:K18985]
109389001  DOCK1; dedicator of cytokinesis protein 1 [KO:K13708]
109380150  RAC1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
109394502  RAC2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]
109393041  RAC3; ras-related C3 botulinum toxin substrate 3 isoform X1 [KO:K07861]
109388601  PIP5K1C; phosphatidylinositol 4-phosphate 5-kinase type-1 gamma isoform X1 [KO:K00889] [EC:2.7.1.68]
109372273  PIP5K1A; phosphatidylinositol 4-phosphate 5-kinase type-1 alpha isoform X1 [KO:K00889] [EC:2.7.1.68]
109392539  PIP5K1B; phosphatidylinositol 4-phosphate 5-kinase type-1 beta isoform X1 [KO:K00889] [EC:2.7.1.68]
109385261  ARF6; ADP-ribosylation factor 6 [KO:K07941]
109372566  WASL; neural Wiskott-Aldrich syndrome protein [KO:K23612]
109379151  ACTR2; actin-related protein 2 isoform X1 [KO:K17260]
109382193  LOW QUALITY PROTEIN: actin-related protein 3B-like [KO:K18584]
109372864  ACTR3; actin-related protein 3 [KO:K18584]
109389641  ACTR3B; actin-related protein 3B [KO:K18584]
109379038  ARPC1A; actin-related protein 2/3 complex subunit 1A [KO:K05757]
109379053  ARPC1B; actin-related protein 2/3 complex subunit 1B [KO:K05757]
109380595  ARPC2; actin-related protein 2/3 complex subunit 2 [KO:K05758]
109386042  ARPC3; actin-related protein 2/3 complex subunit 3 [KO:K05756]
109390824  ARPC4; actin-related protein 2/3 complex subunit 4 [KO:K05755]
109379174  ARPC5; actin-related protein 2/3 complex subunit 5 [KO:K05754]
109391341  ARPC5L; actin-related protein 2/3 complex subunit 5-like protein [KO:K05754]
109376358  actin-related protein 2/3 complex subunit 5 [KO:K05754]
109393048  ACTG1; actin, cytoplasmic 2 [KO:K05692]
109380220  ACTB; actin, cytoplasmic 1 [KO:K05692]
109388728  WIPF1; WAS/WASL-interacting protein family member 1 [KO:K19475]
109380815  WIPF2; WAS/WASL-interacting protein family member 2 [KO:K19475]
109381329  WIPF3; WAS/WASL-interacting protein family member 3 [KO:K19475]
109393032  BAIAP2; brain-specific angiogenesis inhibitor 1-associated protein 2 isoform X1 [KO:K05627]
109386760  WASF2; wiskott-Aldrich syndrome protein family member 2 [KO:K05748]
109386147  paxillin-like [KO:K05760]
109386148  mediator of DNA damage checkpoint protein 1-like [KO:K05760]
109386174  GIT2; ARF GTPase-activating protein GIT2 isoform X1 [KO:K12487]
109383937  ARHGEF7; rho guanine nucleotide exchange factor 7 isoform X1 [KO:K13710]
109396744  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
109374777  WAS; wiskott-Aldrich syndrome protein isoform X1 [KO:K05747]
109385746  guanine nucleotide-binding protein G(q) subunit alpha-like [KO:K04634]
109393895  ARHGEF12; rho guanine nucleotide exchange factor 12 isoform X1 [KO:K07532]
109374465  ARHGEF1; rho guanine nucleotide exchange factor 1 isoform X1 [KO:K12330]
109381903  rho guanine nucleotide exchange factor 28-like [KO:K21072]
109376114  RHOA; transforming protein RhoA isoform X1 [KO:K04513]
109388840  ROCK1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.1]
109386644  ROCK2; rho-associated protein kinase 2 [KO:K17388] [EC:2.7.11.1]
109387051  FYB; FYN-binding protein [KO:K17698]
109381369  SKAP2; src kinase-associated phosphoprotein 2 isoform X1 [KO:K23471]
109377395  NLRP3; NACHT, LRR and PYD domains-containing protein 3 [KO:K12800]
109388792  NLRC4; NLR family CARD domain-containing protein 4 isoform X1 [KO:K12805]
109394244  PKN1; serine/threonine-protein kinase N1 [KO:K06071] [EC:2.7.11.13]
109376724  PKN2; serine/threonine-protein kinase N2 isoform X1 [KO:K23691] [EC:2.7.11.13]
109395688  RPS6KA3; ribosomal protein S6 kinase alpha-3 isoform X1 [KO:K04373] [EC:2.7.11.1]
109386772  RPS6KA1; ribosomal protein S6 kinase alpha-1 isoform X1 [KO:K04373] [EC:2.7.11.1]
109373920  RPS6KA2; ribosomal protein S6 kinase alpha-2 [KO:K04373] [EC:2.7.11.1]
109376759  MEFV; pyrin isoform X1 [KO:K12803]
109385063  LIMK1; LIM domain kinase 1 [KO:K05743] [EC:2.7.11.1]
109374176  PYCARD; apoptosis-associated speck-like protein containing a CARD [KO:K12799]
109377701  CASP1; caspase-1 [KO:K01370] [EC:3.4.22.36]
109388707  IL18; interleukin-18 [KO:K05482]
109393524  IL1B; interleukin-1 beta isoform X1 [KO:K04519]
109385740  TLR4; toll-like receptor 4 [KO:K10160]
109393491  MYD88; myeloid differentiation primary response protein MyD88 [KO:K04729]
109388403  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
109394352  IRAK1; interleukin-1 receptor-associated kinase 1 [KO:K04730] [EC:2.7.11.1]
109381153  TRAF6; TNF receptor-associated factor 6 isoform X1 [KO:K03175] [EC:2.3.2.27]
109381672  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
109392251  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X1 [KO:K04403]
109380888  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
109389465  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
109377344  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
109379632  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
109386279  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
109383860  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
109372541  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
109384322  RELA; transcription factor p65 isoform X1 [KO:K04735]
109385252  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
109388626  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
109385803  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
109394900  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
109390353  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 isoform X1 [KO:K04432] [EC:2.7.12.2]
109371344  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
109395979  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
109395980  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
109396629  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
109396630  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
109389137  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
109396087  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
109392215  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
109377948  mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
109392748  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
109381526  FOS; proto-oncogene c-Fos [KO:K04379]
109371251  JUN; transcription factor AP-1 [KO:K04448]
109371257  transcription factor AP-1 [KO:K04448]
109388568  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
109381695  TBK1; LOW QUALITY PROTEIN: serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
109391076  IRF3; interferon regulatory factor 3 [KO:K05411]
109373073  TNF; tumor necrosis factor isoform X1 [KO:K03156]
109387871  IL6; interleukin-6 [KO:K05405]
109394819  CXCL8; interleukin-8 [KO:K10030]
109396418  IFNB1; interferon beta [KO:K05415]
109381238  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
109394108  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
109372681  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
109382484  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
109395865  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
109373811  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
109381083  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
109385878  RAC-beta serine/threonine-protein kinase-like isoform X1 [KO:K04456] [EC:2.7.11.1]
109374859  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
109385353  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
109388396  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
109373637  CD4; T-cell surface glycoprotein CD4 [KO:K06454]
109375918  CD8A; T-cell surface glycoprotein CD8 alpha chain isoform X1 [KO:K06458]
109376834  CD8B; T-cell surface glycoprotein CD8 beta chain [KO:K06459]
109390746  LCK; tyrosine-protein kinase Lck [KO:K05856] [EC:2.7.10.2]
109390751  tyrosine-protein kinase Lck-like [KO:K05856] [EC:2.7.10.2]
109378262  uncharacterized protein LOC109378262 [KO:K10785]
109391988  tyrosine-protein kinase ZAP-70 [KO:K07360] [EC:2.7.10.2]
109385909  LAT; linker for activation of T-cells family member 1 [KO:K07362]
109379415  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
109381168  VAV2; guanine nucleotide exchange factor VAV2 isoform X1 [KO:K05730]
109374297  guanine nucleotide exchange factor VAV3 [KO:K05730]
109378054  VAV1; proto-oncogene vav [KO:K05730]
109375381  guanine nucleotide exchange factor VAV3-like isoform X1 [KO:K05730]
109379925  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
109383198  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
109381836  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 [KO:K17332]
109389408  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
109395924  IL2; interleukin-2 [KO:K05429]
109374504  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
hai04510  Focal adhesion
hai04620  Toll-like receptor signaling pathway
hai04621  NOD-like receptor signaling pathway
hai04660  T cell receptor signaling pathway
hai04666  Fc gamma R-mediated phagocytosis
hai04810  Regulation of actin cytoskeleton
KO pathway
ko05135   
LinkDB

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