KEGG   PATHWAY: mpah05133
mpah05133                   Pathway                                
Pertussis - Mus pahari (shrew mouse)
Pertussis, also known as whooping cough, is an acute respiratory infectious disease caused by a bacteria called Bordetella Pertussis. The characteristic symptoms are paroxysmal cough, inspiratory wheezing and post-tussive vomiting.
Following the inhalation of respiratory secretions from an infected individual, bacteria enter the upper respiratory tract and adhere to epithelial cells. Several adhesion factors have been implicated: the filamentous hemagglutinin (FHA), fimbriae, and pertactin (Prn).
Pertussis toxin (Ptx) and adenylate cyclase toxin (ACT) have been identified so far as major protein toxins of B. pertussis. PTX is a hexameric AB5-type exotoxin. Catalytic A subunit catalyzes the ADP-ribosylation of the Gi subunits of the heterotrimeric G protein, then inhibits multiple downstream pathways. ACT is able to penetrate the cytoplasmic membrane of host cells and becomes activated through the cleavage and the binding of calmodulin (CaM). Activated ACT converts ATP to cyclic AMP and subverts cellular signaling pathways.
Human Diseases; Infectious disease: bacterial
Pathway map
mpah05133  Pertussis

Mus pahari (shrew mouse) [GN:mpah]
110334621  Itga5; integrin alpha-5 isoform X1 [KO:K06484]
110337225  Itgb1; integrin beta-1 isoform X1 [KO:K05719]
110327528  Itgam; integrin alpha-M isoform X1 [KO:K06461]
110326926  Itgb2; integrin beta-2 [KO:K06464]
110330040  LOW QUALITY PROTEIN: integrin beta-2-like protein [KO:K06464]
110328293  Calml4; calmodulin-like protein 4 isoform X1 [KO:K02183]
110334170  Calml3; calmodulin-like protein 3 [KO:K02183]
110334182  calmodulin-4 [KO:K02183]
110336102  Calm2; calmodulin isoform X1 [KO:K02183]
110324261  Calm1; calmodulin [KO:K02183]
110336466  Calm3; calmodulin [KO:K02183]
110326378  transforming protein RhoA-like isoform X1 [KO:K04513]
110327907  Rhoa; transforming protein RhoA isoform X1 [KO:K04513]
110324632  Cfl2; cofilin-2 [KO:K05765]
110321418  Cfl1; cofilin-1 [KO:K05765]
110336608  Casp3; caspase-3 [KO:K02187] [EC:]
110328167  Casp7; caspase-7 [KO:K04397] [EC:]
110328145  Casp1; caspase-1 [KO:K01370] [EC:]
110333045  apoptosis-associated speck-like protein containing a CARD [KO:K12799]
110332320  Nlrp3; NACHT, LRR and PYD domains-containing protein 3 isoform X1 [KO:K12800]
110319321  Il1b; interleukin-1 beta isoform X1 [KO:K04519]
110323698  C1qa; complement C1q subcomponent subunit A [KO:K03986]
110323604  C1qb; complement C1q subcomponent subunit B [KO:K03987]
110323611  C1qc; complement C1q subcomponent subunit C [KO:K03988]
110314999  complement C1r-A subcomponent-like [KO:K01330] [EC:]
110316472  C1r; complement C1r subcomponent [KO:K01330] [EC:]
110314998  complement C1s subcomponent-like [KO:K01331] [EC:]
110316909  C1s; complement C1s subcomponent [KO:K01331] [EC:]
110336126  C2; complement C2 isoform X1 [KO:K01332] [EC:]
110335909  C4a; complement C4-A isoform X1 [KO:K03989]
110335652  C3; complement C3 [KO:K03990]
110317539  C5; complement C5 [KO:K03994]
110318833  Serping1; plasma protease C1 inhibitor [KO:K04001]
110322103  C4bpa; C4b-binding protein alpha chain [KO:K04002]
110322001  C4bpb; LOW QUALITY PROTEIN: C4b-binding protein beta chain [KO:K04003]
110338918  Ly96; lymphocyte antigen 96 isoform X1 [KO:K05400]
110323586  Tlr4; toll-like receptor 4 [KO:K10160]
110333539  Cd14; monocyte differentiation antigen CD14 [KO:K04391]
110328152  Tirap; toll/interleukin-1 receptor domain-containing adapter protein isoform X1 [KO:K05403]
110327862  Myd88; myeloid differentiation primary response protein MyD88 [KO:K04729]
110334455  Irak4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:]
110313647  Irak1; interleukin-1 receptor-associated kinase 1 isoform X1 [KO:K04730] [EC:]
110318382  Traf6; TNF receptor-associated factor 6 [KO:K03175] [EC:]
110319789  Nfkb1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
110317041  Rela; transcription factor p65 [KO:K04735]
110333036  Ticam2; TIR domain-containing adapter molecule 2 [KO:K05409]
110336092  Ticam1; TIR domain-containing adapter molecule 1 [KO:K05842]
110332836  Irf3; interferon regulatory factor 3 isoform X1 [KO:K05411]
110334495  Mapk11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:]
110337896  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:]
110337946  Mapk14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:]
110334829  Mapk12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:]
110330449  Mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:]
110332652  Mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:]
110325466  Mapk8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:]
110329343  Mapk1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:]
110320020  Mapk3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:]
110324365  Fos; proto-oncogene c-Fos isoform X1 [KO:K04379]
110323252  Jun; transcription factor AP-1 [KO:K04448]
110317140  Il6; interleukin-6 [KO:K05405]
110320680  Il12a; interleukin-12 subunit alpha [KO:K05406]
110332403  Il12b; interleukin-12 subunit beta [KO:K05425]
110327099  Il23a; interleukin-23 subunit alpha [KO:K05426]
110335791  Tnf; tumor necrosis factor isoform X1 [KO:K03156]
110322547  Il10; interleukin-10 [KO:K05443]
110332048  Irf1; interferon regulatory factor 1 isoform X1 [KO:K09444]
110337471  Irf8; interferon regulatory factor 8 [KO:K10155]
110325889  pulmonary surfactant-associated protein A [KO:K10067]
110314435  guanine nucleotide-binding protein G(i) subunit alpha-1 isoform X1 [KO:K04630]
110327202  Gnai2; guanine nucleotide-binding protein G(i) subunit alpha-2 isoform X1 [KO:K04630]
110319821  Gnai3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
110331003  Cxcl6; C-X-C motif chemokine 6 [KO:K05506]
110317065  Nod1; nucleotide-binding oligomerization domain-containing protein 1 [KO:K08727]
110319393  Il1a; interleukin-1 alpha [KO:K04383]
110331408  Nos2; nitric oxide synthase, inducible [KO:K13241] [EC:]
C00002  ATP
C00076  Calcium cation
C00238  Potassium cation
C00253  Nicotinate
C00338  Lipopolysaccharide
C00374  Heparin
C00575  3',5'-Cyclic AMP
C05005  Glycolipid
C12505  Magnesium sulfate
C19596  Lipooligosaccharide
de Gouw D, Diavatopoulos DA, Bootsma HJ, Hermans PW, Mooi FR
Pertussis: a matter of immune modulation.
FEMS Microbiol Rev 35:441-74 (2011)
Carbonetti NH
Pertussis toxin and adenylate cyclase toxin: key virulence factors of Bordetella pertussis and cell biology tools.
Future Microbiol 5:455-69 (2010)
van den Berg BM, van Furth R, Hazenbos WL
Activation of complement receptor 3 on human monocytes by cross-linking of very-late antigen-5 is mediated via protein tyrosine kinases.
Immunology 98:197-202 (1999)
Mazar J, Cotter PA
Topology and maturation of filamentous haemagglutinin suggest a new model for two-partner secretion.
Mol Microbiol 62:641-54 (2006)
Hewlett EL, Donato GM, Gray MC
Macrophage cytotoxicity produced by adenylate cyclase toxin from Bordetella pertussis: more than just making cyclic AMP!
Mol Microbiol 59:447-59 (2006)
Dunne A, Ross PJ, Pospisilova E, Masin J, Meaney A, Sutton CE, Iwakura Y, Tschopp J, Sebo P, Mills KH
Inflammasome activation by adenylate cyclase toxin directs Th17 responses and protection against Bordetella pertussis.
J Immunol 185:1711-9 (2010)
Hickey FB, Brereton CF, Mills KH
Adenylate cycalse toxin of Bordetella pertussis inhibits TLR-induced IRF-1 and IRF-8 activation and IL-12 production and enhances IL-10 through MAPK activation in dendritic cells.
J Leukoc Biol 84:234-43 (2008)
Spensieri F, Fedele G, Fazio C, Nasso M, Stefanelli P, Mastrantonio P, Ausiello CM
Bordetella pertussis inhibition of interleukin-12 (IL-12) p70 in human monocyte-derived dendritic cells blocks IL-12 p35 through adenylate cyclase toxin-dependent cyclic AMP induction.
Infect Immun 74:2831-8 (2006)
Fiser R, Masin J, Basler M, Krusek J, Spulakova V, Konopasek I, Sebo P
Third activity of Bordetella adenylate cyclase (AC) toxin-hemolysin. Membrane translocation of AC domain polypeptide promotes calcium influx into CD11b+ monocytes independently of the catalytic and hemolytic activities.
J Biol Chem 282:2808-20 (2007)
Wang ZY, Yang D, Chen Q, Leifer CA, Segal DM, Su SB, Caspi RR, Howard ZO, Oppenheim JJ
Induction of dendritic cell maturation by pertussis toxin and its B subunit differentially initiate Toll-like receptor 4-dependent signal transduction pathways.
Exp Hematol 34:1115-24 (2006)
Fan H, Peck OM, Tempel GE, Halushka PV, Cook JA
Toll-like receptor 4 coupled GI protein signaling pathways regulate extracellular signal-regulated kinase phosphorylation and AP-1 activation independent of NFkappaB activation.
Shock 22:57-62 (2004)
Lee MS, Kim YJ
Signaling pathways downstream of pattern-recognition receptors and their cross talk.
Annu Rev Biochem 76:447-80 (2007)
Kawai T, Akira S
The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors.
Nat Immunol 11:373-84 (2010)
Ferlito M, Romanenko OG, Guyton K, Ashton S, Squadrito F, Halushka PV, Cook JA
Implication of Galpha i proteins and Src tyrosine kinases in endotoxin-induced signal transduction events and mediator production.
J Endotoxin Res 8:427-35 (2002)
Han HJ, Kuwae A, Abe A, Arakawa Y, Kamachi K
Differential expression of type III effector BteA protein due to IS481 insertion in Bordetella pertussis.
PLoS One 6:e17797 (2011)
Beier D, Gross R
Regulation of bacterial virulence by two-component systems.
Curr Opin Microbiol 9:143-52 (2006)
Cotter PA, Jones AM
Phosphorelay control of virulence gene expression in Bordetella.
Trends Microbiol 11:367-73 (2003)
mpah04010  MAPK signaling pathway
mpah04210  Apoptosis
mpah04610  Complement and coagulation cascades
mpah04620  Toll-like receptor signaling pathway
KO pathway

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