KEGG   PATHWAY: fca05135
Entry
fca05135                    Pathway                                
Name
Yersinia infection - Felis catus (domestic cat)
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
fca05135  Yersinia infection
fca05135

Organism
Felis catus (domestic cat) [GN:fca]
Gene
101081746  FN1; fibronectin isoform X1 [KO:K05717]
101081745  ITGA4; LOW QUALITY PROTEIN: integrin alpha-4 [KO:K06483]
101093870  ITGA5; integrin alpha-5 [KO:K06484]
751821  ITGB1; integrin beta-1 precursor [KO:K05719]
101093337  rho-related GTP-binding protein RhoG-like [KO:K07863]
101087520  RHOG; rho-related GTP-binding protein RhoG [KO:K07863]
101100378  SRC; proto-oncogene tyrosine-protein kinase Src isoform X3 [KO:K05704] [EC:2.7.10.2]
101095952  PTK2; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
101091691  PTK2B; protein-tyrosine kinase 2-beta isoform X2 [KO:K05871] [EC:2.7.10.2]
101084908  CRKL; crk-like protein [KO:K04438]
101086100  CRK; adapter molecule crk isoform X1 [KO:K04438]
101096625  BCAR1; breast cancer anti-estrogen resistance protein 1 isoform X3 [KO:K05726]
101080369  ELMO1; engulfment and cell motility protein 1 isoform X1 [KO:K12366]
101083071  ELMO2; engulfment and cell motility protein 2 isoform X1 [KO:K18985]
101084320  DOCK1; dedicator of cytokinesis protein 1 isoform X1 [KO:K13708]
101101277  RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392]
101096744  RAC2; ras-related C3 botulinum toxin substrate 2 isoform X1 [KO:K07860]
101080496  RAC3; ras-related C3 botulinum toxin substrate 3 isoform X1 [KO:K07861]
101098154  PIP5K1A; LOW QUALITY PROTEIN: phosphatidylinositol 4-phosphate 5-kinase type-1 alpha [KO:K00889] [EC:2.7.1.68]
101081420  PIP5K1B; phosphatidylinositol 4-phosphate 5-kinase type-1 beta isoform X3 [KO:K00889] [EC:2.7.1.68]
101097791  PIP5K1C; phosphatidylinositol 4-phosphate 5-kinase type-1 gamma isoform X1 [KO:K00889] [EC:2.7.1.68]
101093695  ARF6; ADP-ribosylation factor 6 [KO:K07941]
111559482  actin cytoskeleton-regulatory complex protein PAN1-like [KO:K23612]
101095243  WASL; neural Wiskott-Aldrich syndrome protein [KO:K23612]
111557362  uncharacterized protein LOC111557362 [KO:K23612]
101087729  ACTR2; actin-related protein 2 isoform X2 [KO:K17260]
101086891  ACTR3B; actin-related protein 3B isoform X1 [KO:K18584]
101087419  ACTR3; LOW QUALITY PROTEIN: actin-related protein 3 [KO:K18584]
101084410  ARPC1A; actin-related protein 2/3 complex subunit 1A [KO:K05757]
101084672  ARPC1B; actin-related protein 2/3 complex subunit 1B [KO:K05757]
101085911  ARPC2; actin-related protein 2/3 complex subunit 2 [KO:K05758]
101098659  ARPC3; actin-related protein 2/3 complex subunit 3 [KO:K05756]
101084688  ARPC4; actin-related protein 2/3 complex subunit 4 [KO:K05755]
101088207  ARPC5; actin-related protein 2/3 complex subunit 5 [KO:K05754]
101082020  ARPC5L; actin-related protein 2/3 complex subunit 5-like protein [KO:K05754]
100144392  ACTG1; actin, cytoplasmic 2 [KO:K05692]
101098507  ACTB; actin, cytoplasmic 1 [KO:K05692]
101096587  WIPF1; LOW QUALITY PROTEIN: WAS/WASL-interacting protein family member 1 [KO:K19475]
101082534  WIPF2; WAS/WASL-interacting protein family member 2 isoform X1 [KO:K19475]
101094008  WIPF3; WAS/WASL-interacting protein family member 3 [KO:K19475]
101087366  BAIAP2; brain-specific angiogenesis inhibitor 1-associated protein 2 isoform X2 [KO:K05627]
101082837  WASF2; wiskott-Aldrich syndrome protein family member 2 [KO:K05748]
101080922  PXN; paxillin isoform X2 [KO:K05760]
101093054  GIT2; ARF GTPase-activating protein GIT2 isoform X1 [KO:K12487]
101090075  ARHGEF7; rho guanine nucleotide exchange factor 7 isoform X5 [KO:K13710]
101094772  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
101095721  WAS; wiskott-Aldrich syndrome protein isoform X1 [KO:K05747]
101094708  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha isoform X2 [KO:K04634]
101085657  ARHGEF12; rho guanine nucleotide exchange factor 12 isoform X1 [KO:K07532]
101083892  ARHGEF1; rho guanine nucleotide exchange factor 1 isoform X1 [KO:K12330]
101094325  ARHGEF28; rho guanine nucleotide exchange factor 28 isoform X1 [KO:K21072]
101084011  RHOA; transforming protein RhoA [KO:K04513]
101092552  ROCK1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.1]
101094501  ROCK2; rho-associated protein kinase 2 isoform X1 [KO:K17388] [EC:2.7.11.1]
101095954  FYB1; LOW QUALITY PROTEIN: FYN-binding protein 1 [KO:K17698]
101099869  SKAP2; src kinase-associated phosphoprotein 2 [KO:K23471]
101092579  NLRP3; NACHT, LRR and PYD domains-containing protein 3 [KO:K12800]
101087657  NLRC4; NLR family CARD domain-containing protein 4 [KO:K12805]
101097547  PKN1; serine/threonine-protein kinase N1 isoform X1 [KO:K06071] [EC:2.7.11.13]
101081653  PKN2; serine/threonine-protein kinase N2 isoform X1 [KO:K23691] [EC:2.7.11.13]
101082546  RPS6KA3; ribosomal protein S6 kinase alpha-3 isoform X3 [KO:K04373] [EC:2.7.11.1]
101086492  RPS6KA1; ribosomal protein S6 kinase alpha-1 isoform X2 [KO:K04373] [EC:2.7.11.1]
101099466  RPS6KA2; ribosomal protein S6 kinase alpha-2 isoform X1 [KO:K04373] [EC:2.7.11.1]
101094163  RPS6KA6; ribosomal protein S6 kinase alpha-6 [KO:K04373] [EC:2.7.11.1]
101096694  MEFV; pyrin isoform X1 [KO:K12803]
101097861  LIMK1; LIM domain kinase 1 [KO:K05743] [EC:2.7.11.1]
101088449  apoptosis-associated speck-like protein containing a CARD [KO:K12799]
493688  IL18; interleukin-18 precursor [KO:K05482]
768274  IL1B; interleukin-1 beta precursor [KO:K04519]
493698  TLR4; toll-like receptor 4 precursor [KO:K10160]
101087092  MYD88; myeloid differentiation primary response protein MyD88 [KO:K04729]
101100225  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
101090500  IRAK1; interleukin-1 receptor-associated kinase 1 isoform X1 [KO:K04730] [EC:2.7.11.1]
101099750  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
101096363  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
101083606  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X3 [KO:K04403]
101098714  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
101095899  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
101086544  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
101095617  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
100142682  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X2 [KO:K07209] [EC:2.7.11.10]
101090622  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
100142683  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
101096604  RELA; transcription factor p65 [KO:K04735]
101081387  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X2 [KO:K04368] [EC:2.7.12.2]
101100281  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
101087614  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101087958  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
101082274  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
101089813  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
101101135  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
101091536  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
111556320  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
105260786  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
101086432  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
101095157  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
101091310  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
101101463  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
101084765  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
493935  FOS; proto-oncogene c-Fos [KO:K04379]
101097261  JUN; transcription factor AP-1 [KO:K04448]
101082884  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
101091955  TBK1; serine/threonine-protein kinase TBK1 isoform X1 [KO:K05410] [EC:2.7.11.10]
101095934  IRF3; interferon regulatory factor 3 isoform X1 [KO:K05411]
493755  TNF; tumor necrosis factor precursor [KO:K03156]
493687  IL6; interleukin-6 precursor [KO:K05405]
493836  CXCL8; interleukin-8 precursor [KO:K10030]
493849  IFNB1; interferon beta precursor [KO:K05415]
101094274  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101091892  PIK3CB; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
101097413  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
100271864  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X3 [KO:K02649]
101093286  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
101093586  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101087931  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101092818  AKT3; RAC-gamma serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]
100499544  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101081660  GSK3B; glycogen synthase kinase-3 beta isoform X2 [KO:K03083] [EC:2.7.11.26]
100127112  MCP-1; C-C motif chemokine 2 [KO:K14624]
493775  CD4; T-cell surface glycoprotein CD4 precursor [KO:K06454]
493799  CD8A; T-cell surface glycoprotein CD8 alpha chain precursor [KO:K06458]
493948  CD8B; T-cell surface glycoprotein CD8 beta chain precursor [KO:K06459]
101098805  LCK; tyrosine-protein kinase Lck isoform X2 [KO:K05856] [EC:2.7.10.2]
111559549  uncharacterized protein LOC111559549 [KO:K10785]
101097059  tyrosine-protein kinase ZAP-70 isoform X2 [KO:K07360] [EC:2.7.10.2]
101093319  LAT; linker for activation of T-cells family member 1 isoform X1 [KO:K07362]
101096877  LCP2; lymphocyte cytosolic protein 2 isoform X1 [KO:K07361]
101097212  VAV1; proto-oncogene vav isoform X3 [KO:K05730]
101087417  VAV3; guanine nucleotide exchange factor VAV3 [KO:K05730]
101086264  VAV2; guanine nucleotide exchange factor VAV2 isoform X1 [KO:K05730]
101092925  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
101101259  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X3 [KO:K04446]
101080520  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
101083728  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
751114  IL2; interleukin-2 precursor [KO:K05429]
493683  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
  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
fca04510  Focal adhesion
fca04620  Toll-like receptor signaling pathway
fca04621  NOD-like receptor signaling pathway
fca04660  T cell receptor signaling pathway
fca04666  Fc gamma R-mediated phagocytosis
fca04810  Regulation of actin cytoskeleton
KO pathway
ko05135   
LinkDB

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