KEGG   PATHWAY: mmu05135
Entry
mmu05135                    Pathway                                
Name
Yersinia infection - Mus musculus (house mouse)
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
mmu05135  Yersinia infection
mmu05135

Organism
Mus musculus (house mouse) [GN:mmu]
Gene
14268  Fn1; fibronectin 1 [KO:K05717]
16401  Itga4; integrin alpha 4 [KO:K06483]
16402  Itga5; integrin alpha 5 (fibronectin receptor alpha) [KO:K06484]
16412  Itgb1; integrin beta 1 (fibronectin receptor beta) [KO:K05719]
56212  Rhog; ras homolog family member G [KO:K07863]
20779  Src; Rous sarcoma oncogene [KO:K05704] [EC:2.7.10.2]
14083  Ptk2; PTK2 protein tyrosine kinase 2 [KO:K05725] [EC:2.7.10.2]
19229  Ptk2b; PTK2 protein tyrosine kinase 2 beta [KO:K05871] [EC:2.7.10.2]
12928  Crk; v-crk avian sarcoma virus CT10 oncogene homolog [KO:K04438]
12929  Crkl; v-crk avian sarcoma virus CT10 oncogene homolog-like [KO:K04438]
12927  Bcar1; breast cancer anti-estrogen resistance 1 [KO:K05726]
140580  Elmo1; engulfment and cell motility 1 [KO:K12366]
140579  Elmo2; engulfment and cell motility 2 [KO:K18985]
330662  Dock1; dedicator of cytokinesis 1 [KO:K13708]
14131  Fcgr3; Fc receptor, IgG, low affinity III [KO:K06472]
19353  Rac1; Rac family small GTPase 1 [KO:K04392]
19354  Rac2; Rac family small GTPase 2 [KO:K07860]
170758  Rac3; Rac family small GTPase 3 [KO:K07861]
18717  Pip5k1c; phosphatidylinositol-4-phosphate 5-kinase, type 1 gamma [KO:K00889] [EC:2.7.1.68]
18719  Pip5k1b; phosphatidylinositol-4-phosphate 5-kinase, type 1 beta [KO:K00889] [EC:2.7.1.68]
18720  Pip5k1a; phosphatidylinositol-4-phosphate 5-kinase, type 1 alpha [KO:K00889] [EC:2.7.1.68]
11845  Arf6; ADP-ribosylation factor 6 [KO:K07941]
73178  Wasl; WASP like actin nucleation promoting factor [KO:K23612]
66713  Actr2; actin related protein 2 [KO:K17260]
242894  Actr3b; ARP3 actin-related protein 3B [KO:K18584]
74117  Actr3; ARP3 actin-related protein 3 [KO:K18584]
11867  Arpc1b; actin related protein 2/3 complex, subunit 1B [KO:K05757]
56443  Arpc1a; actin related protein 2/3 complex, subunit 1A [KO:K05757]
434782  Gm5637; predicted pseudogene 5637 [KO:K05757]
76709  Arpc2; actin related protein 2/3 complex, subunit 2 [KO:K05758]
56378  Arpc3; actin related protein 2/3 complex, subunit 3 [KO:K05756]
68089  Arpc4; actin related protein 2/3 complex, subunit 4 [KO:K05755]
67771  Arpc5; actin related protein 2/3 complex, subunit 5 [KO:K05754]
74192  Arpc5l; actin related protein 2/3 complex, subunit 5-like [KO:K05754]
11465  Actg1; actin, gamma, cytoplasmic 1 [KO:K05692]
11461  Actb; actin, beta [KO:K05692]
215280  Wipf1; WAS/WASL interacting protein family, member 1 [KO:K19475]
68524  Wipf2; WAS/WASL interacting protein family, member 2 [KO:K19475]
330319  Wipf3; WAS/WASL interacting protein family, member 3 [KO:K19475]
108100  Baiap2; brain-specific angiogenesis inhibitor 1-associated protein 2 [KO:K05627]
242687  Wasf2; WASP family, member 2 [KO:K05748]
19303  Pxn; paxillin [KO:K05760]
26431  Git2; GIT ArfGAP 2 [KO:K12487]
54126  Arhgef7; Rho guanine nucleotide exchange factor [KO:K13710]
12540  Cdc42; cell division cycle 42 [KO:K04393]
22376  Was; Wiskott-Aldrich syndrome [KO:K05747]
14682  Gnaq; guanine nucleotide binding protein, alpha q polypeptide [KO:K04634]
69632  Arhgef12; Rho guanine nucleotide exchange factor 12 [KO:K07532]
16801  Arhgef1; Rho guanine nucleotide exchange factor 1 [KO:K12330]
110596  Arhgef28; Rho guanine nucleotide exchange factor 28 [KO:K21072]
11848  Rhoa; ras homolog family member A [KO:K04513]
67653  4930544G11Rik; RIKEN cDNA 4930544G11 gene [KO:K04513]
19877  Rock1; Rho-associated coiled-coil containing protein kinase 1 [KO:K04514] [EC:2.7.11.1]
19878  Rock2; Rho-associated coiled-coil containing protein kinase 2 [KO:K17388] [EC:2.7.11.1]
23880  Fyb1; FYN binding protein 1 [KO:K17698]
54353  Skap2; src family associated phosphoprotein 2 [KO:K23471]
216799  Nlrp3; NLR family, pyrin domain containing 3 [KO:K12800]
268973  Nlrc4; NLR family, CARD domain containing 4 [KO:K12805]
320795  Pkn1; protein kinase N1 [KO:K06071] [EC:2.7.11.13]
109333  Pkn2; protein kinase N2 [KO:K23691] [EC:2.7.11.13]
110651  Rps6ka3; ribosomal protein S6 kinase polypeptide 3 [KO:K04373] [EC:2.7.11.1]
20111  Rps6ka1; ribosomal protein S6 kinase polypeptide 1 [KO:K04373] [EC:2.7.11.1]
20112  Rps6ka2; ribosomal protein S6 kinase, polypeptide 2 [KO:K04373] [EC:2.7.11.1]
67071  Rps6ka6; ribosomal protein S6 kinase polypeptide 6 [KO:K04373] [EC:2.7.11.1]
54483  Mefv; Mediterranean fever [KO:K12803]
16885  Limk1; LIM domain kinase 1 [KO:K05743] [EC:2.7.11.1]
66824  Pycard; PYD and CARD domain containing [KO:K12799]
12362  Casp1; caspase 1 [KO:K01370] [EC:3.4.22.36]
16173  Il18; interleukin 18 [KO:K05482]
16176  Il1b; interleukin 1 beta [KO:K04519]
21898  Tlr4; toll-like receptor 4 [KO:K10160]
17874  Myd88; myeloid differentiation primary response gene 88 [KO:K04729]
266632  Irak4; interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]
16179  Irak1; interleukin-1 receptor-associated kinase 1 [KO:K04730] [EC:2.7.11.1]
22034  Traf6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
22030  Traf2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
66513  Tab1; TGF-beta activated kinase 1/MAP3K7 binding protein 1 [KO:K04403]
68652  Tab2; TGF-beta activated kinase 1/MAP3K7 binding protein 2 [KO:K04404]
26409  Map3k7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
16151  Ikbkg; inhibitor of kappaB kinase gamma [KO:K07210]
12675  Chuk; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
16150  Ikbkb; inhibitor of kappaB kinase beta [KO:K07209] [EC:2.7.11.10]
18035  Nfkbia; nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha [KO:K04734]
18033  Nfkb1; nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105 [KO:K02580]
19697  Rela; v-rel reticuloendotheliosis viral oncogene homolog A (avian) [KO:K04735]
26395  Map2k1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
26396  Map2k2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
26413  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
26417  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
26397  Map2k3; mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
26399  Map2k6; mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
26416  Mapk14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
19094  Mapk11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
29857  Mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
26415  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
26398  Map2k4; mitogen-activated protein kinase kinase 4 [KO:K04430] [EC:2.7.12.2]
26400  Map2k7; mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
26419  Mapk8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
26420  Mapk9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
26414  Mapk10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
14281  Fos; FBJ osteosarcoma oncogene [KO:K04379]
16476  Jun; jun proto-oncogene [KO:K04448]
106759  Ticam1; TIR domain containing adaptor molecule 1 [KO:K05842]
56480  Tbk1; TANK-binding kinase 1 [KO:K05410] [EC:2.7.11.10]
54131  Irf3; interferon regulatory factor 3 [KO:K05411]
21926  Tnf; tumor necrosis factor [KO:K03156]
16193  Il6; interleukin 6 [KO:K05405]
15977  Ifnb1; interferon beta 1, fibroblast [KO:K05415]
18706  Pik3ca; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
18707  Pik3cd; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
74769  Pik3cb; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
18709  Pik3r2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
18708  Pik3r1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
18710  Pik3r3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
11651  Akt1; thymoma viral proto-oncogene 1 [KO:K04456] [EC:2.7.11.1]
11652  Akt2; thymoma viral proto-oncogene 2 [KO:K04456] [EC:2.7.11.1]
23797  Akt3; thymoma viral proto-oncogene 3 [KO:K04456] [EC:2.7.11.1]
56637  Gsk3b; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
20296  Ccl2; C-C motif chemokine ligand 2 [KO:K14624]
20293  Ccl12; C-C motif chemokine ligand 12 [KO:K14624]
12504  Cd4; CD4 antigen [KO:K06454]
12525  Cd8a; CD8 subunit alpha [KO:K06458]
12526  Cd8b1; CD8 subunit beta 1 [KO:K06459]
16818  Lck; lymphocyte protein tyrosine kinase [KO:K05856] [EC:2.7.10.2]
22637  Zap70; zeta-chain (TCR) associated protein kinase [KO:K07360] [EC:2.7.10.2]
16797  Lat; linker for activation of T cells [KO:K07362]
16822  Lcp2; lymphocyte cytosolic protein 2 [KO:K07361]
22324  Vav1; vav 1 oncogene [KO:K05730]
22325  Vav2; vav 2 oncogene [KO:K05730]
57257  Vav3; vav 3 oncogene [KO:K05730]
18803  Plcg1; phospholipase C, gamma 1 [KO:K01116] [EC:3.1.4.11]
18018  Nfatc1; nuclear factor of activated T cells, cytoplasmic, calcineurin dependent 1 [KO:K04446]
18019  Nfatc2; nuclear factor of activated T cells, cytoplasmic, calcineurin dependent 2 [KO:K17332]
18021  Nfatc3; nuclear factor of activated T cells, cytoplasmic, calcineurin dependent 3 [KO:K17333]
16183  Il2; interleukin 2 [KO:K05429]
16153  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
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
mmu04510  Focal adhesion
mmu04620  Toll-like receptor signaling pathway
mmu04621  NOD-like receptor signaling pathway
mmu04660  T cell receptor signaling pathway
mmu04666  Fc gamma R-mediated phagocytosis
mmu04810  Regulation of actin cytoskeleton
KO pathway
ko05135   
LinkDB

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