KEGG   PATHWAY: elk05135
Entry
elk05135                    Pathway                                
Name
Yersinia infection - Enhydra lutris kenyoni (northern sea otter)
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
elk05135  Yersinia infection
elk05135

Organism
Enhydra lutris kenyoni (northern sea otter) [GN:elk]
Gene
111143733  fibronectin isoform X1 [KO:K05717]
111160297  integrin alpha-4 isoform X1 [KO:K06483]
111157949  integrin alpha-5 isoform X1 [KO:K06484]
111155558  integrin beta-1 isoform X1 [KO:K05719]
111161011  rho-related GTP-binding protein RhoG-like isoform X1 [KO:K07863]
111159459  rho-related GTP-binding protein RhoG [KO:K07863]
111141563  proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
111146744  focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
111153692  protein-tyrosine kinase 2-beta isoform X1 [KO:K05871] [EC:2.7.10.2]
111151533  adapter molecule crk isoform X1 [KO:K04438]
111142678  crk-like protein isoform X1 [KO:K04438]
111152853  breast cancer anti-estrogen resistance protein 1 isoform X1 [KO:K05726]
111147268  engulfment and cell motility protein 1 isoform X1 [KO:K12366]
111141444  engulfment and cell motility protein 2 isoform X1 [KO:K18985]
111145075  dedicator of cytokinesis protein 1 isoform X1 [KO:K13708]
111145636  ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392]
111157484  ras-related C3 botulinum toxin substrate 2 [KO:K07860]
111160304  ras-related C3 botulinum toxin substrate 3 isoform X1 [KO:K07861]
111161951  phosphatidylinositol 4-phosphate 5-kinase type-1 alpha isoform X1 [KO:K00889] [EC:2.7.1.68]
111161679  phosphatidylinositol 4-phosphate 5-kinase type-1 gamma isoform X1 [KO:K00889] [EC:2.7.1.68]
111153502  phosphatidylinositol 4-phosphate 5-kinase type-1 beta [KO:K00889] [EC:2.7.1.68]
111140129  ADP-ribosylation factor 6 [KO:K07941]
111151935  neural Wiskott-Aldrich syndrome protein isoform X1 [KO:K23612]
111147990  actin-related protein 2 isoform X1 [KO:K17260]
111154416  actin-related protein 3B isoform X1 [KO:K18584]
111142734  actin-related protein 3 [KO:K18584]
111145545  actin-related protein 2/3 complex subunit 1A isoform X1 [KO:K05757]
111145659  actin-related protein 2/3 complex subunit 1B [KO:K05757]
111144070  actin-related protein 2/3 complex subunit 2 isoform X1 [KO:K05758]
111156780  LOW QUALITY PROTEIN: actin-related protein 2/3 complex subunit 3-like [KO:K05756]
111156515  actin-related protein 2/3 complex subunit 3 [KO:K05756]
111143772  actin-related protein 2/3 complex subunit 4 isoform X1 [KO:K05755]
111150789  actin-related protein 2/3 complex subunit 5 isoform X1 [KO:K05754]
111146006  actin-related protein 2/3 complex subunit 5-like protein isoform X1 [KO:K05754]
111160249  actin, cytoplasmic 2 [KO:K05692]
111145734  actin, cytoplasmic 1 [KO:K05692]
111145579  WAS/WASL-interacting protein family member 1 [KO:K19475]
111151582  WAS/WASL-interacting protein family member 2 [KO:K19475]
111147292  WAS/WASL-interacting protein family member 3 [KO:K19475]
111160439  brain-specific angiogenesis inhibitor 1-associated protein 2 isoform X1 [KO:K05627]
111142836  wiskott-Aldrich syndrome protein family member 2 [KO:K05748]
111156467  paxillin [KO:K05760]
111156367  ARF GTPase-activating protein GIT2 isoform X1 [KO:K12487]
111146897  rho guanine nucleotide exchange factor 7 isoform X1 [KO:K13710]
111154823  cell division control protein 42 homolog isoform X1 [KO:K04393]
111150530  wiskott-Aldrich syndrome protein [KO:K05747]
111153498  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
111153798  rho guanine nucleotide exchange factor 12 isoform X1 [KO:K07532]
111139489  rho guanine nucleotide exchange factor 1 isoform X1 [KO:K12330]
111148307  rho guanine nucleotide exchange factor 28 [KO:K21072]
111144026  transforming protein RhoA isoform X1 [KO:K04513]
111142435  rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.1]
111154090  rho-associated protein kinase 2 isoform X1 [KO:K17388] [EC:2.7.11.1]
111140907  FYN-binding protein [KO:K17698]
111147284  src kinase-associated phosphoprotein 2 [KO:K23471]
111139817  NACHT, LRR and PYD domains-containing protein 3 isoform X1 [KO:K12800]
111162406  serine/threonine-protein kinase N1 isoform X1 [KO:K06071] [EC:2.7.11.13]
111143223  serine/threonine-protein kinase N2 isoform X1 [KO:K23691] [EC:2.7.11.13]
111139440  ribosomal protein S6 kinase alpha-6 isoform X1 [KO:K04373] [EC:2.7.11.1]
111150451  ribosomal protein S6 kinase alpha-3 isoform X1 [KO:K04373] [EC:2.7.11.1]
111158720  LOW QUALITY PROTEIN: ribosomal protein S6 kinase alpha-2 [KO:K04373] [EC:2.7.11.1]
111154593  ribosomal protein S6 kinase alpha-1 isoform X1 [KO:K04373] [EC:2.7.11.1]
111155992  pyrin isoform X1 [KO:K12803]
111146226  LIM domain kinase 1 isoform X1 [KO:K05743] [EC:2.7.11.1]
111162289  apoptosis-associated speck-like protein containing a CARD isoform X1 [KO:K12799]
111153900  interleukin-18 [KO:K05482]
111158456  interleukin-1 beta [KO:K04519]
111146042  toll-like receptor 4 isoform X1 [KO:K10160]
111159049  myeloid differentiation primary response protein MyD88 [KO:K04729]
111157836  interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
111139109  interleukin-1 receptor-associated kinase 1 isoform X1 [KO:K04730] [EC:2.7.11.1]
111150027  TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
111145476  TNF receptor-associated factor 2-like [KO:K03173] [EC:2.3.2.27]
111146100  TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
111157505  TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
111147521  TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
111158801  mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
111139191  NF-kappa-B essential modulator [KO:K07210]
111144921  inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
111144397  inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
111140276  NF-kappa-B inhibitor alpha isoform X1 [KO:K04734]
111153611  nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
111149956  transcription factor p65 [KO:K04735]
111153158  dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
111161815  dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
111162236  LOW QUALITY PROTEIN: mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
111142759  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
111139240  dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
111158041  dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
111152267  mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
111157625  mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
111157628  mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
111152183  mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
111161210  dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
111161723  dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
111144860  mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
111158897  mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
111154016  mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
111148602  proto-oncogene c-Fos [KO:K04379]
111143174  transcription factor AP-1 [KO:K04448]
111161725  TIR domain-containing adapter molecule 1 [KO:K05842]
111142106  serine/threonine-protein kinase TBK1 isoform X1 [KO:K05410] [EC:2.7.11.10]
111160645  interferon regulatory factor 3 isoform X1 [KO:K05411]
111152248  tumor necrosis factor isoform X1 [KO:K03156]
111147365  interleukin-6 isoform X1 [KO:K05405]
111149115  interleukin-8 [KO:K10030]
111156577  interferon beta [KO:K05415]
111155003  LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
111147545  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
111154641  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
111143470  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
111155224  phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
111143790  phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
111161374  RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
111148765  RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
111150885  RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
111149921  glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
111151532  C-C motif chemokine 2 [KO:K14624]
111159821  T-cell surface glycoprotein CD4 isoform X1 [KO:K06454]
111148035  T-cell surface glycoprotein CD8 alpha chain [KO:K06458]
111148090  T-cell surface glycoprotein CD8 beta chain [KO:K06459]
111142990  tyrosine-protein kinase Lck [KO:K05856] [EC:2.7.10.2]
111155922  tyrosine-protein kinase ZAP-70 [KO:K07360] [EC:2.7.10.2]
111162219  linker for activation of T-cells family member 1 isoform X1 [KO:K07362]
111140829  lymphocyte cytosolic protein 2 [KO:K07361]
111146429  guanine nucleotide exchange factor VAV2 isoform X1 [KO:K05730]
111161665  proto-oncogene vav isoform X1 [KO:K05730]
111142837  guanine nucleotide exchange factor VAV3 [KO:K05730]
111141423  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
111154209  nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
111141582  LOW QUALITY PROTEIN: nuclear factor of activated T-cells, cytoplasmic 2 [KO:K17332]
111152752  nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
111154869  interleukin-2 [KO:K05429]
111151100  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
elk04510  Focal adhesion
elk04620  Toll-like receptor signaling pathway
elk04621  NOD-like receptor signaling pathway
elk04660  T cell receptor signaling pathway
elk04666  Fc gamma R-mediated phagocytosis
elk04810  Regulation of actin cytoskeleton
KO pathway
ko05135   
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