Listeria monocytogenes entry into host cells (Homo sapiens)

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4-6, 10-12, 172215, 18153, 16142147, 92141, 2, 18Host cellListeria monocytogenesplasma membraneHost cellcytosolcell wallSH3GL3 UBC(305-380) p-Y-CTNNB1 UBC(229-304) UBC(609-684) STAM2 Ca2+ UBC(305-380) InlB SH3KBP1 UBC(1-76) InlB UBC(609-684) UBC(381-456) p-Y-CBL MonoUb-K,p-Y1234,Y1235,Y1349,Y1356-MET UBC(77-152) METRPS27A(1-76) UBC(77-152) UBA52(1-76) InlB:p-4Y-METdimer:GRB2-1:p-Y-CBLZn2+ RPS27A(1-76) ATPp-Y753,Y754-CDH1(155-882) UBC(305-380) InlB:MonoUb-K,p-4Y-MET:GRB2-1:p-Y-CBL:CIN85:endophilin:EPS15:HGS:STAMUBC(457-532) EPS15 SH3GL3 InlB CTNNB1 UBC(1-76) UBB(1-76) InlA:Ub-K,p-Y753,Y754-CDH1:Ub-K,p-Y-CTNNB1:CBLL1 dimer:Zn2+UBB(153-228) GRB2-1 UBB(153-228) InlA InlB UbUBC(381-456) InlB UBB(77-152) GRB2-1 p-Y-CBL UBC(1-76) UBB(1-76) UBC(229-304) UBB(77-152) CBL ATPCa2+ CIN85:endophilinCDH1(155-882) MET UBC(1-76) CDH1(155-882) UBA52(1-76) UBB(1-76) Ca2+ UBC(153-228) STAM STAM2 MyrG-SRCUBC(609-684) GRB2-1 UBB(153-228) SH3GL2 ADPSTAM InlA:p-Y753,Y754-CDH1:p-Y-CTNNB1:CBLL1 dimer:Zn2+GRB2-1 Ca2+ UBC(1-76) HGS UBB(77-152) Zn2+ p-Y-CBL p-Y753,Y754-CDH1(155-882) UBC(77-152) HGS UBC(381-456) InlA CTNND1UBA52(1-76) UBC(153-228) MonoUb-K,p-Y1234,Y1235,Y1349,Y1356-MET SH3GL1 UBC(533-608) CTNND1 SH3KBP1 p-Y1234,Y1235,Y1349,Y1356-MET UBC(77-152) ADPUBC(381-456) ADPUBA52(1-76) Ca2+ SH3GL2 InlBCDH1:CTNNB1:CTNND1ADPUBC(609-684) UBB(153-228) CBLL1 dimer:Zn2+CTNND1 InlB RPS27A(1-76) UBC(229-304) Ub-K,p-Y-CTNNB1 InlB:p-4Y-MET dimerUb-K,p-Y753,Y754-CDH1(155-882) GRB2-1 SH3KBP1 InlB UBC(153-228) MonoUb-K,p-Y1234,Y1235,Y1349,Y1356-MET ATPInlB EPS15:HGS:STAMp-Y-CBL p-Y-CTNNB1 InlB UBC(305-380) SH3GL1 UBC(457-532) InlB p-Y1234,Y1235,Y1349,Y1356-MET CTNND1 CBLL1 MyrG-p-Y419-SRCSH3GL3 MET InlB InlB InlB:METUBC(457-532) UBC(153-228) UBB(77-152) InlB UBC(229-304) SH3GL2 UBC(457-532) InlB ATPCBL UBB(1-76) InlB:MonoUb-K,p-4Y-MET dimer:GRB2-1:p-Y-CBL:CIN85:endophilinUBC(533-608) UBC(457-532) RPS27A(1-76) InlB UBB(1-76) UBC(533-608) CTNNB1 EPS15 UBC(153-228) InlB:MonoUb-K,p-4Y-MET dimer:GRB2-1:p-Y-CBLInlB p-Y1234,Y1235,Y1349,Y1356-MET UBC(305-380) UBC(609-684) UBB(77-152) UBB(153-228) InlAInlB:p-4Y-METdimer:GRB2-1:CBLUBC(533-608) UBC(381-456) Zn2+ InlB RPS27A(1-76) InlA:p-Y753,Y754-CDH1:p-Y-CTNNB1:CTNND1InlB:MET dimerInlA:CDH1:CTNNB1:CTNND1InlB GRB2-1 InlA UBC(77-152) CBLL1 UBC(533-608) CBL:GRB2CBLL1 SH3GL1 UBC(229-304) UBA52(1-76) InlA 1371521, 2, 188


Description

Listeria monocytogenes is a short, gram-positive, nonspore-forming motile rod. Serotypes 1/2a, 1/2b and 4b make up more than 95% of isolates from humans, with serotype 4b causing most of the food-borne outbreaks. Listeria monocytogenes enters the body through the gastrointestinal tract after ingestion of contaminated food. The bacteria can survive food preservation procedures, such as refrigeration, low pH and high salt.
Listeria monocytogenes expresses several adhesin proteins at the cell surface that facilitate bacterial binding and entry to host cells. The bacteria can enter host cells through endocytosis mediated by binding of the bacterial InlA (internalin) protein to CDH1 (E-cadherin) at the host cell plasma membrane. Listeria monocytogenes can also enter host cells through endocytosis mediated by binding of the bacterial InlB protein to MET receptor tyrosine kinase at the host cell plasma membrane. Listeria monocytogenes proliferates inside the host cells and triggers formation of filopods, elongated protrusions of the host plasma membrane that contain bacteria. Filopods are ingested by adjacent cells, allowing Listeria monocytogenes to spread from cell to cell, invisible to the immune system of the host.
Listeria monocytogenes can cross the intestinal, blood-brain and placental barriers. In immunocompetent adults Listeria monocytogenes infection usually causes gastroenteritis. In infants infected in utero and in immunocompromised adults Listeria monocytogenes infection can result in meningoencephalitis and bacteremia (sepsis).
InlA is critical for crossing the intestinal barrier while both InlA and InlB are needed for crossing the placental barrier (Gessain et al. 2015) and, based on in vitro studies, the blood-cerebrospinal fluid barrier (Grundler et al. 2013). It seems that the intrinsic level of PI3K activity in Listeria-targeted host cells determines whether the entry depends on InlA only or InlA and InlB. The interaction of InlA with E-cadherin does not activate PI3K/AKT signaling while the interaction of InlB with the MET receptor activated the PI3K/AKT signal transduction cascade. Therefore, InlB-MET interaction may be important in tissues with low intrinsic PI3K activity (Gessain et al. 2015). Even if InlA-E-cadherin route is sufficient for bacterial entry, InlB may accelerate bacterial invasion (Pentecost et al. 2010). Cholesterol levels in host cell plasma membrane may also influence the preferred route for bacterial endocytosis (Seveau et al. 2004). In addition to InlA and InlB, many other virulence factors are involved in the Listeria monocytogenes infection cycle (Camejo et al. 2011) and will be annotated as mechanistic details become available.
For review, please refer to Bonazzi et al. 2009, Brooks et al. 2010, Camejo et al. 2011, Pizarro-Cerda et al. 2012. View original pathway at Reactome.

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Pathway is converted from Reactome ID: 8876384
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Reactome version: 75
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Reactome Author: Orlic-Milacic, Marija

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Bibliography

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  1. Shen Y, Naujokas M, Park M, Ireton K.; ''InIB-dependent internalization of Listeria is mediated by the Met receptor tyrosine kinase.''; PubMed Europe PMC Scholia
  2. Veiga E, Cossart P.; ''Listeria hijacks the clathrin-dependent endocytic machinery to invade mammalian cells.''; PubMed Europe PMC Scholia
  3. Brown MT, Cooper JA.; ''Regulation, substrates and functions of src.''; PubMed Europe PMC Scholia
  4. Pizarro-Cerdá J, Kühbacher A, Cossart P.; ''Entry of Listeria monocytogenes in mammalian epithelial cells: an updated view.''; PubMed Europe PMC Scholia
  5. Seveau S, Bierne H, Giroux S, Prévost MC, Cossart P.; ''Role of lipid rafts in E-cadherin-- and HGF-R/Met--mediated entry of Listeria monocytogenes into host cells.''; PubMed Europe PMC Scholia
  6. Pentecost M, Kumaran J, Ghosh P, Amieva MR.; ''Listeria monocytogenes internalin B activates junctional endocytosis to accelerate intestinal invasion.''; PubMed Europe PMC Scholia
  7. Mengaud J, Ohayon H, Gounon P, Mege R-M, Cossart P.; ''E-cadherin is the receptor for internalin, a surface protein required for entry of L. monocytogenes into epithelial cells.''; PubMed Europe PMC Scholia
  8. Mukherjee M, Chow SY, Yusoff P, Seetharaman J, Ng C, Sinniah S, Koh XW, Asgar NF, Li D, Yim D, Jackson RA, Yew J, Qian J, Iyu A, Lim YP, Zhou X, Sze SK, Guy GR, Sivaraman J.; ''Structure of a novel phosphotyrosine-binding domain in Hakai that targets E-cadherin.''; PubMed Europe PMC Scholia
  9. Lecuit M, Dramsi S, Gottardi C, Fedor-Chaiken M, Gumbiner B, Cossart P.; ''A single amino acid in E-cadherin responsible for host specificity towards the human pathogen Listeria monocytogenes.''; PubMed Europe PMC Scholia
  10. Camejo A, Carvalho F, Reis O, Leitão E, Sousa S, Cabanes D.; ''The arsenal of virulence factors deployed by Listeria monocytogenes to promote its cell infection cycle.''; PubMed Europe PMC Scholia
  11. Gründler T, Quednau N, Stump C, Orian-Rousseau V, Ishikawa H, Wolburg H, Schroten H, Tenenbaum T, Schwerk C.; ''The surface proteins InlA and InlB are interdependently required for polar basolateral invasion by Listeria monocytogenes in a human model of the blood-cerebrospinal fluid barrier.''; PubMed Europe PMC Scholia
  12. Gessain G, Tsai YH, Travier L, Bonazzi M, Grayo S, Cossart P, Charlier C, Disson O, Lecuit M.; ''PI3-kinase activation is critical for host barrier permissiveness to Listeria monocytogenes.''; PubMed Europe PMC Scholia
  13. Bache KG, Raiborg C, Mehlum A, Stenmark H.; ''STAM and Hrs are subunits of a multivalent ubiquitin-binding complex on early endosomes.''; PubMed Europe PMC Scholia
  14. Bonazzi M, Veiga E, Pizarro-Cerdá J, Cossart P.; ''Successive post-translational modifications of E-cadherin are required for InlA-mediated internalization of Listeria monocytogenes.''; PubMed Europe PMC Scholia
  15. Ferraris DM, Gherardi E, Di Y, Heinz DW, Niemann HH.; ''Ligand-mediated dimerization of the Met receptor tyrosine kinase by the bacterial invasion protein InlB.''; PubMed Europe PMC Scholia
  16. Sousa S, Cabanes D, Bougnères L, Lecuit M, Sansonetti P, Tran-Van-Nhieu G, Cossart P.; ''Src, cortactin and Arp2/3 complex are required for E-cadherin-mediated internalization of Listeria into cells.''; PubMed Europe PMC Scholia
  17. Bonazzi M, Lecuit M, Cossart P.; ''Listeria monocytogenes internalin and E-cadherin: from structure to pathogenesis.''; PubMed Europe PMC Scholia
  18. Niemann HH, Jäger V, Butler PJ, van den Heuvel J, Schmidt S, Ferraris D, Gherardi E, Heinz DW.; ''Structure of the human receptor tyrosine kinase met in complex with the Listeria invasion protein InlB.''; PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
114762view16:25, 25 January 2021ReactomeTeamReactome version 75
113206view11:27, 2 November 2020ReactomeTeamReactome version 74
112430view15:37, 9 October 2020ReactomeTeamReactome version 73
101334view11:22, 1 November 2018ReactomeTeamreactome version 66
100872view20:55, 31 October 2018ReactomeTeamreactome version 65
100413view19:29, 31 October 2018ReactomeTeamreactome version 64
99962view16:13, 31 October 2018ReactomeTeamreactome version 63
99517view14:47, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99159view12:41, 31 October 2018ReactomeTeamreactome version 62
93619view11:28, 9 August 2017ReactomeTeamNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
ADPMetaboliteCHEBI:456216 (ChEBI)
ATPMetaboliteCHEBI:30616 (ChEBI)
CBL ProteinP22681 (Uniprot-TrEMBL)
CBL:GRB2ComplexR-HSA-182910 (Reactome)
CBLL1 ProteinQ75N03 (Uniprot-TrEMBL)
CBLL1 dimer:Zn2+ComplexR-HSA-8876991 (Reactome)
CDH1(155-882) ProteinP12830 (Uniprot-TrEMBL)
CDH1:CTNNB1:CTNND1ComplexR-HSA-8877851 (Reactome)
CIN85:endophilinComplexR-HSA-8875480 (Reactome)
CTNNB1 ProteinP35222 (Uniprot-TrEMBL)
CTNND1 ProteinO60716 (Uniprot-TrEMBL)
CTNND1ProteinO60716 (Uniprot-TrEMBL)
Ca2+ MetaboliteCHEBI:29108 (ChEBI)
EPS15 ProteinP42566 (Uniprot-TrEMBL)
EPS15:HGS:STAMComplexR-HSA-182947 (Reactome)
GRB2-1 ProteinP62993-1 (Uniprot-TrEMBL)
HGS ProteinO14964 (Uniprot-TrEMBL)
InlA ProteinP0DJM0 (Uniprot-TrEMBL)
InlA:CDH1:CTNNB1:CTNND1ComplexR-HSA-8876504 (Reactome)
InlA:Ub-K,p-Y753,Y754-CDH1:Ub-K,p-Y-CTNNB1:CBLL1 dimer:Zn2+ComplexR-HSA-8877010 (Reactome)
InlA:p-Y753,Y754-CDH1:p-Y-CTNNB1:CBLL1 dimer:Zn2+ComplexR-HSA-8876983 (Reactome)
InlA:p-Y753,Y754-CDH1:p-Y-CTNNB1:CTNND1ComplexR-HSA-8876941 (Reactome)
InlAProteinP0DJM0 (Uniprot-TrEMBL)
InlB ProteinP0DQD2 (Uniprot-TrEMBL)
InlB ProteinP0DQD3 (Uniprot-TrEMBL)
InlB:MET dimerComplexR-HSA-8876211 (Reactome)
InlB:METComplexR-HSA-8875370 (Reactome)
InlB:MonoUb-K,p-4Y-MET dimer:GRB2-1:p-Y-CBL:CIN85:endophilinComplexR-HSA-8876251 (Reactome)
InlB:MonoUb-K,p-4Y-MET dimer:GRB2-1:p-Y-CBLComplexR-HSA-8876253 (Reactome)
InlB:MonoUb-K,p-4Y-MET:GRB2-1:p-Y-CBL:CIN85:endophilin:EPS15:HGS:STAMComplexR-HSA-8876263 (Reactome)
InlB:p-4Y-MET dimer:GRB2-1:CBLComplexR-HSA-8876242 (Reactome)
InlB:p-4Y-MET dimer:GRB2-1:p-Y-CBLComplexR-HSA-8876247 (Reactome)
InlB:p-4Y-MET dimerComplexR-HSA-8876231 (Reactome)
InlBComplexR-LMO-9637757 (Reactome)
MET ProteinP08581 (Uniprot-TrEMBL)
METProteinP08581 (Uniprot-TrEMBL)
MonoUb-K,p-Y1234,Y1235,Y1349,Y1356-MET ProteinP08581 (Uniprot-TrEMBL)
MyrG-SRCProteinP12931 (Uniprot-TrEMBL)
MyrG-p-Y419-SRCProteinP12931 (Uniprot-TrEMBL)
RPS27A(1-76) ProteinP62979 (Uniprot-TrEMBL)
SH3GL1 ProteinQ99961 (Uniprot-TrEMBL)
SH3GL2 ProteinQ99962 (Uniprot-TrEMBL)
SH3GL3 ProteinQ99963 (Uniprot-TrEMBL)
SH3KBP1 ProteinQ96B97 (Uniprot-TrEMBL)
STAM ProteinQ92783 (Uniprot-TrEMBL)
STAM2 ProteinO75886 (Uniprot-TrEMBL)
UBA52(1-76) ProteinP62987 (Uniprot-TrEMBL)
UBB(1-76) ProteinP0CG47 (Uniprot-TrEMBL)
UBB(153-228) ProteinP0CG47 (Uniprot-TrEMBL)
UBB(77-152) ProteinP0CG47 (Uniprot-TrEMBL)
UBC(1-76) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(153-228) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(229-304) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(305-380) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(381-456) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(457-532) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(533-608) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(609-684) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(77-152) ProteinP0CG48 (Uniprot-TrEMBL)
Ub-K,p-Y-CTNNB1 ProteinP35222 (Uniprot-TrEMBL)
Ub-K,p-Y753,Y754-CDH1(155-882) ProteinP12830 (Uniprot-TrEMBL)
UbComplexR-HSA-113595 (Reactome)
Zn2+ MetaboliteCHEBI:29105 (ChEBI)
p-Y-CBL ProteinP22681 (Uniprot-TrEMBL)
p-Y-CTNNB1 ProteinP35222 (Uniprot-TrEMBL)
p-Y1234,Y1235,Y1349,Y1356-MET ProteinP08581 (Uniprot-TrEMBL)
p-Y753,Y754-CDH1(155-882) ProteinP12830 (Uniprot-TrEMBL)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
ADPArrowR-HSA-112333 (Reactome)
ADPArrowR-HSA-8876230 (Reactome)
ADPArrowR-HSA-8876246 (Reactome)
ADPArrowR-HSA-8876948 (Reactome)
ATPR-HSA-112333 (Reactome)
ATPR-HSA-8876230 (Reactome)
ATPR-HSA-8876246 (Reactome)
ATPR-HSA-8876948 (Reactome)
CBL:GRB2R-HSA-8876240 (Reactome)
CBLL1 dimer:Zn2+R-HSA-8876993 (Reactome)
CDH1:CTNNB1:CTNND1R-HSA-8876497 (Reactome)
CIN85:endophilinR-HSA-8876255 (Reactome)
CTNND1ArrowR-HSA-8876993 (Reactome)
EPS15:HGS:STAMR-HSA-8876262 (Reactome)
InlA:CDH1:CTNNB1:CTNND1ArrowR-HSA-112333 (Reactome)
InlA:CDH1:CTNNB1:CTNND1ArrowR-HSA-8876497 (Reactome)
InlA:CDH1:CTNNB1:CTNND1R-HSA-8876948 (Reactome)
InlA:Ub-K,p-Y753,Y754-CDH1:Ub-K,p-Y-CTNNB1:CBLL1 dimer:Zn2+ArrowR-HSA-8877003 (Reactome)
InlA:p-Y753,Y754-CDH1:p-Y-CTNNB1:CBLL1 dimer:Zn2+ArrowR-HSA-8876993 (Reactome)
InlA:p-Y753,Y754-CDH1:p-Y-CTNNB1:CBLL1 dimer:Zn2+R-HSA-8877003 (Reactome)
InlA:p-Y753,Y754-CDH1:p-Y-CTNNB1:CBLL1 dimer:Zn2+mim-catalysisR-HSA-8877003 (Reactome)
InlA:p-Y753,Y754-CDH1:p-Y-CTNNB1:CTNND1ArrowR-HSA-8876948 (Reactome)
InlA:p-Y753,Y754-CDH1:p-Y-CTNNB1:CTNND1R-HSA-8876993 (Reactome)
InlAR-HSA-8876497 (Reactome)
InlB:MET dimerArrowR-HSA-8876210 (Reactome)
InlB:MET dimerR-HSA-8876230 (Reactome)
InlB:MET dimermim-catalysisR-HSA-8876230 (Reactome)
InlB:METArrowR-HSA-8875371 (Reactome)
InlB:METR-HSA-8876210 (Reactome)
InlB:MonoUb-K,p-4Y-MET dimer:GRB2-1:p-Y-CBL:CIN85:endophilinArrowR-HSA-8876255 (Reactome)
InlB:MonoUb-K,p-4Y-MET dimer:GRB2-1:p-Y-CBL:CIN85:endophilinR-HSA-8876262 (Reactome)
InlB:MonoUb-K,p-4Y-MET dimer:GRB2-1:p-Y-CBLArrowR-HSA-8876258 (Reactome)
InlB:MonoUb-K,p-4Y-MET dimer:GRB2-1:p-Y-CBLR-HSA-8876255 (Reactome)
InlB:MonoUb-K,p-4Y-MET:GRB2-1:p-Y-CBL:CIN85:endophilin:EPS15:HGS:STAMArrowR-HSA-8876262 (Reactome)
InlB:p-4Y-MET dimer:GRB2-1:CBLArrowR-HSA-8876240 (Reactome)
InlB:p-4Y-MET dimer:GRB2-1:CBLR-HSA-8876246 (Reactome)
InlB:p-4Y-MET dimer:GRB2-1:CBLmim-catalysisR-HSA-8876246 (Reactome)
InlB:p-4Y-MET dimer:GRB2-1:p-Y-CBLArrowR-HSA-8876246 (Reactome)
InlB:p-4Y-MET dimer:GRB2-1:p-Y-CBLR-HSA-8876258 (Reactome)
InlB:p-4Y-MET dimer:GRB2-1:p-Y-CBLmim-catalysisR-HSA-8876258 (Reactome)
InlB:p-4Y-MET dimerArrowR-HSA-8876230 (Reactome)
InlB:p-4Y-MET dimerR-HSA-8876240 (Reactome)
InlBR-HSA-8875371 (Reactome)
METR-HSA-8875371 (Reactome)
MyrG-SRCR-HSA-112333 (Reactome)
MyrG-SRCmim-catalysisR-HSA-112333 (Reactome)
MyrG-p-Y419-SRCArrowR-HSA-112333 (Reactome)
MyrG-p-Y419-SRCmim-catalysisR-HSA-8876948 (Reactome)
R-HSA-112333 (Reactome) SRC activation involves autophosphorylation at tyrosine residue Y419 (Brown and Cooper 1996). Binding of the Listeria monocytogenes cell wall protein InlA to E-cadherin (CDH1) triggers SRC autophosphorylation at Y419 through an unknown mechanism (Sousa et al. 2007). CDH1 engagement (adhesion) at cell-cell contacts is also known to induce SRC autophosphorylation (Fujita et al. 2002, McLachlan et al. 2007) and may involve integrins (Avizienyte et al. 2002, Martinez-Rico et al. 2010), but the process has not been fully elucidated.
R-HSA-8875371 (Reactome) InlB, a cell wall protein of Listeria monocytogenes, binds MET receptor, acting as an HGF agonist. InlB interacts with the extracellular portion of MET via two interfaces: the leucine rich repeat region (LRR) of InlB interacts with the Ig1 repeat of MET, while the inter-repeat (IR) region of InlB interacts with the Sema domain of MET (Shen et al. 2000, Veiga and Cossart 2005, Niemann et al. 2007).
R-HSA-8876210 (Reactome) Listeria monocytogenes InlB proteins dimerize through their leucine-rich repeat regions (LRRs), promoting dimerization of their associated MET receptors (Ferraris et al. 2010).
R-HSA-8876230 (Reactome) MET bound to Listeria monocytogenes InlB protein undergoes trans-autophosphorylation. Phosphorylation at tyrosine residues Y1234 and Y1235 in the activation loop of the kinase domain of MET was specifically demonstrated. As InlB-activated MET activates downstream signaling by ERKs (MAPKs) and PI3K/AKT, MET is presumably phosphorylated on GRB2 and GAB1 docking sites Y1349 and Y1356, respectively (Niemann et al. 2007, Ferraris et al. 2010).
R-HSA-8876240 (Reactome) GRB2 is needed for the recruitment of CBL to the complex of Listeria monocytogenes InlB protein and phosphorylated MET receptor (Veiga and Cossart 2005).
R-HSA-8876246 (Reactome) Binding of InlB to MET receptor induces CBL phosphorylation on tyrosine residue(s). Based on the analogy with HGF-induced MET signaling, MET receptor activated by binding of the Listeria monocytogenes protein InlB phosphorylates CBL, promoting stronger interaction of CBL with MET (Peschard et al. 2001, Petrelli et al. 2002).
R-HSA-8876255 (Reactome) CIN85 is necessary for endocytosis-mediated entry of Listeria monocytogenes triggered by CBL-mediated monoubiquitination of MET receptor activated by binding to the bacterial cell wall protein InlB (Veiga et al. 2005). Based on the analogy with HGF-activated MET signaling (Petrelli et al. 2002), CBL recruits the complex of CIN85 and endophilin to Listeria-engaged MET.
R-HSA-8876258 (Reactome) CBL promotes monoubiquitination of MET receptor that is activated by binding of the Listeria monocytogenes cell wall protein InlB. CBL-mediated monoubiquitination of MET promotes endocytosis and entry of Listeria monocytogenes into host cells (Veiga and Cossart 2005).
R-HSA-8876262 (Reactome) Proteins involved in clathrin-mediated endocytosis EPS15 and HGS (Hrs) are both necessary for CBL and MET-mediated entry of Listeria monocytogenes into host cells (Veiga and Cossart 2005). Based on the analogy with HGF-activated MET signaling (Bache et al. 2003, Row et al. 2005, Parachoniak et al. 2009), HGS and EPS15, in complex with STAM proteins, bind to MET receptor monoubiquitinated by CBL upon MET receptor activation by the Listeria monocytogenes InlB protein.
R-HSA-8876497 (Reactome) Internalin (InlA), a cell wall protein of Listeria monocytogenes, binds to the E-cadherin (CDH1) complex at the plasma membrane of the host cell, triggering bacterial entry (Mengaud et al. 1996). The first extracellular domain (EC1) of CDH1 is involved in InlA binding, with proline residue P16 being critical for the interaction (Lecuit et al. 1999).
R-HSA-8876948 (Reactome) SRC-mediated phosphorylation of E-cadherin (CDH1) is needed for InlA-mediated entry of Listeria monocytogenes into host cells (Bonazzi et al. 2008). At cell adhesion sites, SRC is known to phosphorylate CDH1 at tyrosine residues Y753 and Y754 and CDH1-bound beta-catenin (CTNNB1) at an unknown tyrosine residue. SRC-phosphorylated tyrosines of CDH1 and CTNNB1 serve as docking sites for the E3 ubiquitin ligase Hakai (CBLL1) (Fujita et al. 2002, Mukherjee et al. 2012).
R-HSA-8876993 (Reactome) CBL-like E3 ubiquitin ligase Hakai (CBLL1) binds to SRC-phosphorylated E-cadherin (CDH1) complex bound to Listeria monocytogenes cell wall protein InlA (Bonazzi et al. 2008). SRC-mediated phosphorylation of CDH1 complex on tyrosine residues Y753 and Y754 of CDH1 and an unknown tyrosine of beta-catenin (CTNNB1) at cell-cell adhesion sites creates docking sites for CBLL1. CBLL1 functions as zinc (Zn2+) coordinated homodimer. While CBLL1 interacts simultaneously with CDH1 and CTNNB1, CTNND1 (p120 catenin) is displaced by CBLL1 binding (Fujita et al. 2002, Mukherjee et al. 2012).
R-HSA-8877003 (Reactome) CBL-like E3 ubiquitin ligase Hakai (CBLL1) ubiquitinates the E-cadherin complex engaged by binding of E-cadherin (CDH1) to internalin (InlA), a cell wall protein of Listeria monocytogenes. CBLL1 ubiquitinates both CDH1 and CDH1-bound beta-catenin (CTNNB1), triggering endocytosis of the InlA-bound CDH1 complex and entry of bacteria to host cells. It appears that both clathrin-mediated and caveolin-mediated endocytosis contribute to invasion of host cells by Listeria monocytogenes via the InlA-CDH1 route (Bonazzi et al. 2008).
CBLL1 may undergo SRC-mediated phosphorylation and subsequent auto-ubiquitination (Fujita et al. 2002).
UbR-HSA-8876258 (Reactome)
UbR-HSA-8877003 (Reactome)
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