KEGG   PATHWAY: fca05135
fca05135                    Pathway                                
Yersinia infection - Felis catus (domestic cat)
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.
Human Diseases; Infectious disease: bacterial
Pathway map
fca05135  Yersinia infection

Felis catus (domestic cat) [GN:fca]
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:]
101095952  PTK2; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:]
101091691  PTK2B; protein-tyrosine kinase 2-beta isoform X2 [KO:K05871] [EC:]
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:]
101081420  PIP5K1B; phosphatidylinositol 4-phosphate 5-kinase type-1 beta isoform X3 [KO:K00889] [EC:]
101097791  PIP5K1C; phosphatidylinositol 4-phosphate 5-kinase type-1 gamma isoform X1 [KO:K00889] [EC:]
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:]
101094501  ROCK2; rho-associated protein kinase 2 isoform X1 [KO:K17388] [EC:]
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:]
101081653  PKN2; serine/threonine-protein kinase N2 isoform X1 [KO:K23691] [EC:]
101082546  RPS6KA3; ribosomal protein S6 kinase alpha-3 isoform X3 [KO:K04373] [EC:]
101086492  RPS6KA1; ribosomal protein S6 kinase alpha-1 isoform X2 [KO:K04373] [EC:]
101099466  RPS6KA2; ribosomal protein S6 kinase alpha-2 isoform X1 [KO:K04373] [EC:]
101094163  RPS6KA6; ribosomal protein S6 kinase alpha-6 [KO:K04373] [EC:]
101096694  MEFV; pyrin isoform X1 [KO:K12803]
101097861  LIMK1; LIM domain kinase 1 [KO:K05743] [EC:]
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:]
101090500  IRAK1; interleukin-1 receptor-associated kinase 1 isoform X1 [KO:K04730] [EC:]
101099750  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:]
101096363  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:]
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:]
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:]
100142682  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X2 [KO:K07209] [EC:]
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:]
101100281  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:]
101087614  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:]
101087958  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:]
101082274  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:]
101089813  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:]
101101135  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:]
101091536  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:]
111556320  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:]
105260786  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:]
101086432  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:]
101095157  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:]
101091310  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:]
101101463  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:]
101084765  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:]
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:]
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:]
101091892  PIK3CB; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:]
101097413  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:]
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:]
101092818  AKT3; RAC-gamma serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:]
100499544  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:]
101081660  GSK3B; glycogen synthase kinase-3 beta isoform X2 [KO:K03083] [EC:]
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:]
111559549  uncharacterized protein LOC111559549 [KO:K10785]
101097059  tyrosine-protein kinase ZAP-70 isoform X2 [KO:K07360] [EC:]
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:]
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]
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
Pha K, Navarro L
Yersinia type III effectors perturb host innate immune responses.
World J Biol Chem 7:1-13 (2016)
Pinaud L, Sansonetti PJ, Phalipon A
Host Cell Targeting by Enteropathogenic Bacteria T3SS Effectors.
Trends Microbiol 26:266-283 (2018)
Huveneers S, Danen EH
Adhesion signaling - crosstalk between integrins, Src and Rho.
J Cell Sci 122:1059-69 (2009)
Angot A, Vergunst A, Genin S, Peeters N
Exploitation of eukaryotic ubiquitin signaling pathways by effectors translocated by bacterial type III and type IV secretion systems.
PLoS Pathog 3:e3 (2007)
Bliska JB
Yop effectors of Yersinia spp. and actin rearrangements.
Trends Microbiol 8:205-8 (2000)
Gustavsson A, Yuan M, Fallman M
Temporal dissection of beta1-integrin signaling indicates a role for p130Cas-Crk in filopodia formation.
J Biol Chem 279:22893-901 (2004)
Bruce-Staskal PJ, Weidow CL, Gibson JJ, Bouton AH
Cas, Fak and Pyk2 function in diverse signaling cascades to promote Yersinia uptake.
J Cell Sci 115:2689-700 (2002)
McGee K, Zettl M, Way M, Fallman M
A role for N-WASP in invasin-promoted internalisation.
FEBS Lett 509:59-65 (2001)
Pizarro-Cerda J, Cossart P
Subversion of phosphoinositide metabolism by intracellular bacterial pathogens.
Nat Cell Biol 6:1026-33 (2004)
Chung LK, Park YH, Zheng Y, Brodsky IE, Hearing P, Kastner DL, Chae JJ, Bliska JB
The Yersinia Virulence Factor YopM Hijacks Host Kinases to Inhibit Type III Effector-Triggered Activation of the Pyrin Inflammasome.
Cell Host Microbe 20:296-306 (2016)
Schotte P, Denecker G, Van Den Broeke A, Vandenabeele P, Cornelis GR, Beyaert R
Targeting Rac1 by the Yersinia effector protein YopE inhibits caspase-1-mediated maturation and release of interleukin-1beta.
J Biol Chem 279:25134-42 (2004)
Orth K, Palmer LE, Bao ZQ, Stewart S, Rudolph AE, Bliska JB, Dixon JE
Inhibition of the mitogen-activated protein kinase kinase superfamily by a Yersinia effector.
Science 285:1920-3 (1999)
Zhou H, Monack DM, Kayagaki N, Wertz I, Yin J, Wolf B, Dixit VM
Yersinia virulence factor YopJ acts as a deubiquitinase to inhibit NF-kappa B activation.
J Exp Med 202:1327-32 (2005)
Haase R, Richter K, Pfaffinger G, Courtois G, Ruckdeschel K
Yersinia outer protein P suppresses TGF-beta-activated kinase-1 activity to impair innate immune signaling in Yersinia enterocolitica-infected cells.
J Immunol 175:8209-17 (2005)
Thiefes A, Wolf A, Doerrie A, Grassl GA, Matsumoto K, Autenrieth I, Bohn E, Sakurai H, Niedenthal R, Resch K, Kracht M
The Yersinia enterocolitica effector YopP inhibits host cell signalling by inactivating the protein kinase TAK1 in the IL-1 signalling pathway.
EMBO Rep 7:838-44 (2006)
Rosadini CV, Zanoni I, Odendall C, Green ER, Paczosa MK, Philip NH, Brodsky IE, Mecsas J, Kagan JC
A Single Bacterial Immune Evasion Strategy Dismantles Both MyD88 and TRIF Signaling Pathways Downstream of TLR4.
Cell Host Microbe 18:682-93 (2015)
Rolan HG, Durand EA, Mecsas J
Identifying Yersinia YopH-targeted signal transduction pathways that impair neutrophil responses during in vivo murine infection.
Cell Host Microbe 14:306-17 (2013)
Alonso A, Bottini N, Bruckner S, Rahmouni S, Williams S, Schoenberger SP, Mustelin T
Lck dephosphorylation at Tyr-394 and inhibition of T cell antigen receptor signaling by Yersinia phosphatase YopH.
J Biol Chem 279:4922-8 (2004)
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

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