KEGG   PATHWAY: ray05135
Entry
ray05135                    Pathway                                
Name
Yersinia infection - Rousettus aegyptiacus (Egyptian rousette)
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
ray05135  Yersinia infection
ray05135

Organism
Rousettus aegyptiacus (Egyptian rousette) [GN:ray]
Gene
107513401  FN1; LOW QUALITY PROTEIN: fibronectin [KO:K05717]
107520625  ITGA4; integrin alpha-4 [KO:K06483]
107521082  ITGA5; integrin alpha-5 isoform X1 [KO:K06484]
107499295  ITGB1; integrin beta-1 isoform X1 [KO:K05719]
107513866  rho-related GTP-binding protein RhoG-like [KO:K07863]
107517366  RHOG; rho-related GTP-binding protein RhoG [KO:K07863]
107512598  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
107504408  PTK2; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
107515459  PTK2B; protein-tyrosine kinase 2-beta isoform X1 [KO:K05871] [EC:2.7.10.2]
107507729  CRK; adapter molecule crk isoform X1 [KO:K04438]
107497859  CRKL; crk-like protein [KO:K04438]
107502656  BCAR1; breast cancer anti-estrogen resistance protein 1 isoform X1 [KO:K05726]
107518261  ELMO1; engulfment and cell motility protein 1 [KO:K12366]
107498284  ELMO2; engulfment and cell motility protein 2 [KO:K18985]
107512566  DOCK1; LOW QUALITY PROTEIN: dedicator of cytokinesis protein 1 [KO:K13708]
107507577  Ig heavy chain Mem5-like [KO:K06856]
107502475  low affinity immunoglobulin gamma Fc region receptor II-a-like [KO:K06472]
107515925  RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392]
107519267  RAC2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]
107520254  RAC3; ras-related C3 botulinum toxin substrate 3 [KO:K07861]
107520114  PIP5K1C; LOW QUALITY PROTEIN: phosphatidylinositol 4-phosphate 5-kinase type-1 gamma [KO:K00889] [EC:2.7.1.68]
107505403  PIP5K1B; phosphatidylinositol 4-phosphate 5-kinase type-1 beta isoform X1 [KO:K00889] [EC:2.7.1.68]
107498996  PIP5K1A; phosphatidylinositol 4-phosphate 5-kinase type-1 alpha isoform X1 [KO:K00889] [EC:2.7.1.68]
107511431  ARF6; ADP-ribosylation factor 6 [KO:K07941]
107500211  WASL; neural Wiskott-Aldrich syndrome protein [KO:K23612]
107518315  ACTR2; actin-related protein 2 isoform X1 [KO:K17260]
107520306  ACTR3B; actin-related protein 3B isoform X1 [KO:K18584]
107516501  ACTR3; actin-related protein 3 [KO:K18584]
107517854  ARPC1B; actin-related protein 2/3 complex subunit 1B [KO:K05757]
107517855  ARPC1A; LOW QUALITY PROTEIN: actin-related protein 2/3 complex subunit 1A [KO:K05757]
107516729  ARPC2; actin-related protein 2/3 complex subunit 2 [KO:K05758]
107513242  ARPC3; actin-related protein 2/3 complex subunit 3 isoform X1 [KO:K05756]
107504870  ARPC4; actin-related protein 2/3 complex subunit 4 [KO:K05755]
107506642  ARPC5L; actin-related protein 2/3 complex subunit 5-like protein [KO:K05754]
107511298  ARPC5; actin-related protein 2/3 complex subunit 5 [KO:K05754]
107520262  ACTG1; actin, cytoplasmic 2 [KO:K05692]
107515934  ACTB; actin, cytoplasmic 1 [KO:K05692]
107505015  WIPF1; WAS/WASL-interacting protein family member 1 [KO:K19475]
107520674  WIPF2; WAS/WASL-interacting protein family member 2 [KO:K19475]
107505689  WIPF3; LOW QUALITY PROTEIN: WAS/WASL-interacting protein family member 3 [KO:K19475]
107510096  BAIAP2; brain-specific angiogenesis inhibitor 1-associated protein 2 isoform X1 [KO:K05627]
107503537  WASF2; wiskott-Aldrich syndrome protein family member 2 [KO:K05748]
107501228  paxillin isoform X1 [KO:K05760]
107500134  GIT2; ARF GTPase-activating protein GIT2 isoform X1 [KO:K12487]
107511123  ARHGEF7; rho guanine nucleotide exchange factor 7 isoform X1 [KO:K13710]
107513058  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
107515028  WAS; wiskott-Aldrich syndrome protein isoform X1 [KO:K05747]
107517194  GNAQ; LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
107513342  ARHGEF12; rho guanine nucleotide exchange factor 12 [KO:K07532]
107502587  ARHGEF1; rho guanine nucleotide exchange factor 1 isoform X1 [KO:K12330]
107498707  ARHGEF28; rho guanine nucleotide exchange factor 28 [KO:K21072]
107513350  RHOA; transforming protein RhoA [KO:K04513]
107520580  ROCK1; rho-associated protein kinase 1 [KO:K04514] [EC:2.7.11.1]
107501194  ROCK2; LOW QUALITY PROTEIN: rho-associated protein kinase 2 [KO:K17388] [EC:2.7.11.1]
107512431  FYB; FYN-binding protein [KO:K17698]
107505664  SKAP2; src kinase-associated phosphoprotein 2 [KO:K23471]
107500359  NLRP3; NACHT, LRR and PYD domains-containing protein 3 isoform X1 [KO:K12800]
107505750  NLRC4; NLR family CARD domain-containing protein 4 isoform X1 [KO:K12805]
107519425  PKN1; serine/threonine-protein kinase N1 isoform X1 [KO:K06071] [EC:2.7.11.13]
107512704  PKN2; serine/threonine-protein kinase N2 isoform X1 [KO:K23691] [EC:2.7.11.13]
107503561  RPS6KA1; ribosomal protein S6 kinase alpha-1 isoform X1 [KO:K04373] [EC:2.7.11.1]
107519754  RPS6KA6; ribosomal protein S6 kinase alpha-6 isoform X1 [KO:K04373] [EC:2.7.11.1]
107501695  RPS6KA2; ribosomal protein S6 kinase alpha-2 isoform X1 [KO:K04373] [EC:2.7.11.1]
107500168  RPS6KA3; ribosomal protein S6 kinase alpha-3 isoform X1 [KO:K04373] [EC:2.7.11.1]
107498781  MEFV; pyrin isoform X1 [KO:K12803]
107502841  LIMK1; LIM domain kinase 1 [KO:K05743] [EC:2.7.11.1]
107503994  PYCARD; apoptosis-associated speck-like protein containing a CARD [KO:K12799]
107504293  CASP1; caspase-1 isoform X1 [KO:K01370] [EC:3.4.22.36]
107512960  IL18; LOW QUALITY PROTEIN: interleukin-18 [KO:K05482]
107514900  IL1B; interleukin-1 beta isoform X1 [KO:K04519]
107514466  TLR4; toll-like receptor 4 isoform X1 [KO:K10160]
107499600  MYD88; myeloid differentiation primary response protein MyD88 [KO:K04729]
107511752  IRAK4; interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]
107517734  IRAK1; interleukin-1 receptor-associated kinase 1 [KO:K04730] [EC:2.7.11.1]
107499247  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
107503081  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
107500809  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
107518453  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404]
107508648  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
107499585  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
107499756  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
107501353  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
107514416  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
107517900  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
107497522  RELA; transcription factor p65 [KO:K04735]
107508942  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
107510634  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
107515836  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
107497830  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
107506757  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 isoform X1 [KO:K04432] [EC:2.7.12.2]
107510279  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
107497883  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
107497895  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
107500264  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
107500274  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
107517401  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
107519926  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
107512328  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
107509910  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
107515392  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
107498912  FOS; proto-oncogene c-Fos [KO:K04379]
107518352  JUN; transcription factor AP-1 [KO:K04448]
107510780  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
107508222  TBK1; serine/threonine-protein kinase TBK1 isoform X1 [KO:K05410] [EC:2.7.11.10]
107498821  IRF3; interferon regulatory factor 3 isoform X1 [KO:K05411]
107498497  TNF; tumor necrosis factor [KO:K03156]
107518120  IL6; interleukin-6 isoform X1 [KO:K05405]
107515317  C-X-C motif chemokine 15-like [KO:K10030]
107515319  CXCL8; interleukin-8 [KO:K10030]
107518589  IFNB1; interferon beta [KO:K05415]
107520152  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
107517828  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
107513958  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
107521668  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
107517899  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
107498704  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
107513978  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
107521783  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
107498395  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
107517741  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
107519955  C-C motif chemokine 2-like [KO:K14624]
107505973  CD8A; T-cell surface glycoprotein CD8 alpha chain [KO:K06458]
107505939  CD8B; T-cell surface glycoprotein CD8 beta chain [KO:K06459]
107513587  LCK; tyrosine-protein kinase Lck isoform X1 [KO:K05856] [EC:2.7.10.2]
107516945  uncharacterized protein LOC107516945 [KO:K10785]
107509971  tyrosine-protein kinase ZAP-70 [KO:K07360] [EC:2.7.10.2]
107515810  LAT; linker for activation of T-cells family member 1 [KO:K07362]
107518466  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
107502025  guanine nucleotide exchange factor VAV2-like [KO:K05730]
107511258  VAV1; proto-oncogene vav isoform X1 [KO:K05730]
107518292  VAV3; guanine nucleotide exchange factor VAV3 isoform X1 [KO:K05730]
107506741  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
107500851  NFATC1; LOW QUALITY PROTEIN: nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446]
107510349  nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
107498687  nuclear factor of activated T-cells, cytoplasmic 2-like isoform X1 [KO:K17332]
107520480  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
107505383  IL2; interleukin-2 isoform X1 [KO:K05429]
107502233  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
ray04510  Focal adhesion
ray04620  Toll-like receptor signaling pathway
ray04621  NOD-like receptor signaling pathway
ray04660  T cell receptor signaling pathway
ray04666  Fc gamma R-mediated phagocytosis
ray04810  Regulation of actin cytoskeleton
KO pathway
ko05135   
LinkDB

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