KEGG   PATHWAY: ko05135
Entry
ko05135                     Pathway                                
Name
Yersinia infection
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
ko05135  Yersinia infection
ko05135

Disease
H00298  Yersiniosis
Orthology
K00889  PIP5K; 1-phosphatidylinositol-4-phosphate 5-kinase [EC:2.7.1.68]
K00922  PIK3CA_B_D; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153]
K01116  PLCG1; phosphatidylinositol phospholipase C, gamma-1 [EC:3.1.4.11]
K01370  CASP1; caspase 1 [EC:3.4.22.36]
K02580  NFKB1; nuclear factor NF-kappa-B p105 subunit
K02649  PIK3R1_2_3; phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K03083  GSK3B; glycogen synthase kinase 3 beta [EC:2.7.11.26]
K03156  TNF, TNFA; tumor necrosis factor superfamily, member 2
K03173  TRAF2; TNF receptor-associated factor 2 [EC:2.3.2.27]
K03175  TRAF6; TNF receptor-associated factor 6 [EC:2.3.2.27]
K04368  MAP2K1, MEK1; mitogen-activated protein kinase kinase 1 [EC:2.7.12.2]
K04369  MAP2K2, MEK2; mitogen-activated protein kinase kinase 2 [EC:2.7.12.2]
K04371  ERK, MAPK1_3; mitogen-activated protein kinase 1/3 [EC:2.7.11.24]
K04373  RPS6KA; ribosomal protein S6 kinase alpha-1/2/3/6 [EC:2.7.11.1]
K04379  FOS; proto-oncogene protein c-fos
K04392  RAC1; Ras-related C3 botulinum toxin substrate 1
K04393  CDC42; cell division control protein 42
K04403  MAP3K7IP1, TAB1; TAK1-binding protein 1
K04404  MAP3K7IP2, TAB2; TAK1-binding protein 2
K04427  MAP3K7, TAK1; mitogen-activated protein kinase kinase kinase 7 [EC:2.7.11.25]
K04430  MAP2K4, MKK4; mitogen-activated protein kinase kinase 4 [EC:2.7.12.2]
K04431  MAP2K7, MKK7; mitogen-activated protein kinase kinase 7 [EC:2.7.12.2]
K04432  MAP2K3, MKK3; mitogen-activated protein kinase kinase 3 [EC:2.7.12.2]
K04433  MAP2K6, MKK6; mitogen-activated protein kinase kinase 6 [EC:2.7.12.2]
K04438  CRK, CRKII; C-crk adapter molecule crk
K04440  JNK; mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24]
K04441  P38; p38 MAP kinase [EC:2.7.11.24]
K04446  NFATC1, NFAT2, NFATC; nuclear factor of activated T-cells, cytoplasmic 1
K04448  JUN; transcription factor AP-1
K04456  AKT; RAC serine/threonine-protein kinase [EC:2.7.11.1]
K04467  IKBKA, IKKA, CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10]
K04513  RHOA; Ras homolog gene family, member A
K04514  ROCK1; Rho-associated protein kinase 1 [EC:2.7.11.39]
K04519  IL1B; interleukin 1 beta
K04634  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha
K04729  MYD88; myeloid differentiation primary response protein MyD88
K04730  IRAK1; interleukin-1 receptor-associated kinase 1 [EC:2.7.11.1]
K04733  IRAK4; interleukin-1 receptor-associated kinase 4 [EC:2.7.11.1]
K04734  NFKBIA; NF-kappa-B inhibitor alpha
K04735  RELA; transcription factor p65
K05405  IL6; interleukin 6
K05410  TBK1; TANK-binding kinase 1 [EC:2.7.11.10]
K05411  IRF3; interferon regulatory factor 3
K05415  IFNB; interferon beta
K05429  IL2; interleukin 2
K05443  IL10, CSIF; interleukin 10
K05482  IL18, IL1F4; interleukin 18
K05627  BAIAP2, IRSP53; BAI1-associated protein 2
K05692  ACTB_G1; actin beta/gamma 1
K05704  SRC; tyrosine-protein kinase Src [EC:2.7.10.2]
K05717  FN1; fibronectin 1
K05719  ITGB1, CD29; integrin beta 1
K05725  PTK2, FAK; focal adhesion kinase 1 [EC:2.7.10.2]
K05726  BCAR1, CAS; breast cancer anti-estrogen resistance 1
K05730  VAV; guanine nucleotide exchange factor VAV
K05743  LIMK1; LIM domain kinase 1 [EC:2.7.11.1]
K05747  WAS; Wiskott-Aldrich syndrome protein
K05748  WASF2; WAS protein family, member 2
K05754  ARPC5; actin related protein 2/3 complex, subunit 5
K05755  ARPC4; actin related protein 2/3 complex, subunit 4
K05756  ARPC3; actin related protein 2/3 complex, subunit 3
K05757  ARPC1A_B; actin related protein 2/3 complex, subunit 1A/1B
K05758  ARPC2; actin related protein 2/3 complex, subunit 2
K05760  PXN; paxillin
K05842  TRIF; toll-like receptor adapter molecule 1
K05856  LCK; lymphocyte cell-specific protein tyrosine kinase [EC:2.7.10.2]
K05871  PTK2B, FAK2; focal adhesion kinase 2 [EC:2.7.10.2]
K06071  PKN1; serine/threonine-protein kinase N1 [EC:2.7.11.13]
K06454  CD4; T-cell surface glycoprotein CD4
K06458  CD8A; T-cell surface glycoprotein CD8 alpha chain
K06459  CD8B; T-cell surface glycoprotein CD8 beta chain
K06472  FCGR2A, CD32; low affinity immunoglobulin gamma Fc receptor II-a
K06483  ITGA4, CD49d; integrin alpha 4
K06484  ITGA5, CD49e; integrin alpha 5
K06856  IGH; immunoglobulin heavy chain
K07209  IKBKB, IKKB; inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10]
K07210  IKBKG, IKKG, NEMO; inhibitor of nuclear factor kappa-B kinase subunit gamma
K07360  ZAP70; tyrosine-protein kinase ZAP-70 [EC:2.7.10.2]
K07361  LCP2; lymphocyte cytosolic protein 2
K07362  LAT; linker for activation of T cells family member 1
K07532  ARHGEF12, LARG; Rho guanine nucleotide exchange factor 12
K07860  RAC2; Ras-related C3 botulinum toxin substrate 2
K07861  RAC3; Ras-related C3 botulinum toxin substrate 3
K07863  RHOG; Ras homolog gene family, member G
K07941  ARF6; ADP-ribosylation factor 6
K08598  yopJ; YopJ protease family
K08599  yopT; YopT peptidase [EC:3.4.22.-]
K10030  IL8, CXCL8; interleukin 8
K10160  TLR4, CD284; toll-like receptor 4
K10784  TRAV; T cell receptor alpha chain V region
K10785  TRBV; T-cell receptor beta chain V region
K12330  ARHGEF1; Rho guanine nucleotide exchange factor 1
K12341  yadA; adhesin YadA
K12366  ELMO1, CED12; engulfment and cell motility protein 1
K12487  GIT2; G protein-coupled receptor kinase interactor 2
K12799  PYCARD, ASC; apoptosis-associated speck-like protein containing a CARD
K12800  NLRP3, PYPAF1; NACHT, LRR and PYD domains-containing protein 3
K12803  MEFV; pyrin
K12805  NLRC4, CARD12; NLR family CARD domain-containing protein 4
K13708  DOCK1; dedicator of cytokinesis protein 1
K13710  ARHGEF7, PIXB; Rho guanine nucleotide exchange factor 7
K13735  yeeJ; adhesin/invasin
K14624  CCL2, MCP1; C-C motif chemokine 2
K17260  ACTR2, ARP2; actin-related protein 2
K17332  NFATC2, NFAT1, NFATP; nuclear factor of activated T-cells, cytoplasmic 2
K17333  NFATC3, NFAT4; nuclear factor of activated T-cells, cytoplasmic 3
K17388  ROCK2; Rho-associated protein kinase 2 [EC:2.7.11.39]
K17698  FYB, ADAP; FYN binding protein
K18584  ACTR3, ARP3; actin-related protein 3
K18985  ELMO2, CED12A; engulfment and cell motility protein 2
K19475  WIPF; WAS/WASL-interacting protein
K21072  ARHGEF28; A-kinase anchor protein 28
K23471  SKAP2; src kinase-associated phosphoprotein 2
K23472  ypkA, yopO; serine/threonine protein kinase YpkA
K23473  yopE; outer membrane virulence protein YopE
K23474  yopH; tyrosine-protein phosphatase YopH
K23475  yopB, popB, aopB; transloator
K23476  yopD, popD, aopD; transloator
K23477  yopQ, yopK; protein YopQ
K23478  yopM; outer membrane protein YopM
K23612  WASL; neural Wiskott-Aldrich syndrome protein
K23691  PKN2; serine/threonine-protein kinase N2
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
PMID:26981193
  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
PMID:29477730
  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
PMID:19339545
  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
PMID:17257058
  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
PMID:10785635
  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
PMID:15044442
  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
PMID:12077360
  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
PMID:11734206
  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
PMID:15516995
  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
PMID:27569559
  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
PMID:15060067
  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
PMID:10489373
  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
PMID:16301742
  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
PMID:16339560
  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
PMID:16845370
  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
PMID:26651944
  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
PMID:24034616
  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
PMID:14623872
  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
ko03070  Bacterial secretion system
ko04510  Focal adhesion
ko04620  Toll-like receptor signaling pathway
ko04621  NOD-like receptor signaling pathway
ko04660  T cell receptor signaling pathway
ko04666  Fc gamma R-mediated phagocytosis
ko04810  Regulation of actin cytoskeleton

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