MyD88:MAL(TIRAP) cascade initiated on plasma membrane (Homo sapiens)

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825, 64336, 21, 5942, 43687, 51, 55, 743, 11, 40, 41, 52...31, 35, 48, 5018, 21, 241, 331, 3, 34, 45, 68...14, 30, 58, 6531, 35, 48, 507813, 36, 632, 5, 22, 23, 38...71174, 13, 56, 6315, 49, 67, 713361, 623, 11, 771, 3316, 51, 749, 32, 5633, 52cytosolTLR6 TIRAP ATPPI(4,5)P2 TRAF6:p-IRAK2:p-IRAK4:oligo-MyD88:TIRAP:activated TLRLPS 4xPalmC-CD36 LPS BTK Lipoteichoic acid TLR6 Diacyl lipopeptide Clostridial peptidoglycan TAB3 BTK TLR1 Diacyl lipopeptide ADPTAK1 complexIKBKG 2xN4GlycoAsn-TLR4 p-IRAK2 p-IRAK2:oligo-TRAF6TLR2 TLR2 MYD88 TLR1 PI(4,5)P2 K63polyUbIRAK2 2xN4GlycoAsn-LY96 TRAF6:p-IRAK2p-T184,T187-MAP3K7 RPS27A(1-76) PI(4,5)P2 K63polyUb-hp-IRAK1 IRAK1/orIRAK2:p-IRAK4:MyD88oligomer:TIRAP:activated TLRPI(4,5)P22xN4GlycoAsn-TLR4 Clostridial peptidoglycan 2xN4GlycoAsn-LY96 TRAF6 oligo-MyD88:TIRAP:BTK:activated TLRTLR1 Activated TLR1:2 orTLR 2:6heterodimers orTLR4 homodimerIRAK4 Lipoteichoic acid p-IRAK2:p-IRAK4:oligo-MyD88:TIRAP:activated TLRClostridial peptidoglycan CD14(20-345) BTK 2xN4GlycoAsn-TLR4 Clostridial peptidoglycan Major outer membrane protein P CD14(20-345) 2xN4GlycoAsn-LY96 UBB(77-152) TLR6 p-PELI3 BTK IRAK4:oligo-MyD88:TIRAP:activated TLRTLR2 4xPalmC-CD36 TLR6 Clostridial peptidoglycan MYD88 UBC(381-456) UBC(609-684) TLR1 Lipoteichoic acid CHUK ADPTLR2 GPIN-CD14(20-345) p-4Y-TIRAP UBC(77-152) TLR2 Lipoteichoic acid GPIN-CD14(20-345) Triacyl lipopeptide p-2S,S376,T,T209,T387-IRAK1 LPS Clostridial peptidoglycan LPS MYD88 p-4Y-TIRAP TAB1 UBB(153-228) LPS Clostridial peptidoglycan 2xN4GlycoAsn-TLR4 ECSITK63polyUb LPS p-S,2T-IRAK4:oligo-MyD88:TIRAP:activated TLR receptorp-IRAK2 IKBKB TIRAP:PI(4,5)P2:BTK:activated TLR2/4TLR6 Major outer membrane protein P 4xPalmC-CD36 UBC(1-76) IRAK1 2xN4GlycoAsn-TLR4 TIRAP TLR1 2xN4GlycoAsn-TLR4 TIRAP:PI(4,5)P2:activated TLR2/4K63-linked polyUbp-IRAK1:TRAF6Triacyl lipopeptide Lipoteichoic acid Triacyl lipopeptide TLR6 Triacyl lipopeptide TLR2 TLR2 TRAF6 4xPalmC-CD36 ATPBTK TLR1 Diacyl lipopeptide Clostridial peptidoglycan 4xPalmC-CD36 p-PELI1 2xN4GlycoAsn-LY96 ATPMajor outer membrane protein P UBA52(1-76) CD14(20-345) TLR1 CD14(20-345) BTK Major outer membrane protein P Triacyl lipopeptide Diacyl lipopeptide p-T342,T345,S346-IRAK4 4xPalmC-CD36 p-IRAK2:K63-linkedpUboligo-TRAF6:freeK63-linkedpUb:p-TAK1complexSOCS1TLR6 p-IRAK2:K63-linkedpUboligo-TRAF6:freeK63 pUb:TAK1complexp-4Y-TIRAP Diacyl lipopeptide CD14(20-345) Lipoteichoic acid TLR2 Clostridial peptidoglycan ATPDiacyl lipopeptide PI(4,5)P2 IRAK3Lipoteichoic acid p-2S,S376,T,T209,T387-IRAK1 p-4Y-TIRAP 4xPalmC-CD36 Major outer membrane protein P TLR2 Major outer membrane protein P p-4Y-TIRAP Triacyl lipopeptide Major outer membrane protein P p-IRAK2 Diacyl lipopeptide BTK Major outer membrane protein P 2xN4GlycoAsn-LY96 Clostridial peptidoglycan GPIN-CD14(20-345) MYD88 TRAF6 TAB3 PI(4,5)P2 PI(4,5)P2 TRAF6:K63-linkedpolyUb p-IRAK1:IKKcomplexp-2S,S376,T,T209,T387-IRAK1 TLR1 Clostridial peptidoglycan Triacyl lipopeptide p-T342,T345,S346-IRAK4 p-T209,T387-IRAK1 p-3S,3T-IRAK1:p-S,2T-IRAK4:oligo-MyD88:TIRAP:activated TLRp-PELI1 MYD88 Major outer membrane protein P p-T342,T345,S346-IRAK4 TLR2 BTKp-IRAK2 GPIN-CD14(20-345) LPS 2xN4GlycoAsn-LY96 TLR2 MYD88 4xPalmC-CD36 IRAK1 p-T342,T345,S346-IRAK4 TRAF6 CHUK:IKBKB:IKBKGLipoteichoic acid 2xN4GlycoAsn-LY96 TLR6 2xN4GlycoAsn-TLR4 BTK Lipoteichoic acid UbCD14(20-345) BTK IRAK2 ATPTriacyl lipopeptide IRAK4TLR6 BTK TLR2 TLR6 LPS BTK TLR1 ADPTAB1 Lipoteichoic acid TAB1 ATPCD14(20-345) UBC(305-380) Major outer membrane protein P p-4Y-TIRAP 4xPalmC-CD36 Lipoteichoic acid LPS Triacyl lipopeptide CD14(20-345) Triacyl lipopeptide MYD88 IKBKG CD14(20-345) MYD88 K63polyUb-TRAF6 MyD88:TIRAP:BTK:activated TLR2/4p-2S,S376,T,T209,T387-IRAK1 CD14(20-345) p-PELI2 2xN4GlycoAsn-LY96 Triacyl lipopeptide Diacyl lipopeptide K63polyUb-hp-IRAK1 PI(4,5)P2 UBC(153-228) TIRAP:PI(4,5)P2BTK GPIN-CD14(20-345) MYD88 TLR6 4xPalmC-CD36 PI(4,5)P2 CD14(20-345) MYD88TRAF6Major outer membrane protein P p-PELI1 IKBKB p-4Y-TIRAP activatedTLR2/4:p-4Y-TIRAP:PI(4,5)P2:BTK4xPalmC-CD36 Lipoteichoic acid TRAF6 TRAF6 2xN4GlycoAsn-LY96 Triacyl lipopeptide GPIN-CD14(20-345) 4xPalmC-CD36 Major outer membrane protein P ATPTLR6 UBC(229-304) TLR6 Lipoteichoic acid TLR1 IRAK1:p-S,2T-IRAK4:oligo-MyD88:TIRAP:activated TLRMYD88 TRAF6UBC(457-532) Lipoteichoic acid p-IRAK2:K63-linkedpUb oligo-TRAF6TLR1 MAP3K12xN4GlycoAsn-TLR4 PI(4,5)P2 TLR1 4xPalmC-CD36 Lipoteichoic acid TLR1 TRAF6 p-PELI2 GPIN-CD14(20-345) p-4Y-TIRAP GPIN-CD14(20-345) p-IRAK2 TLR2 IRAK4 Diacyl lipopeptide UBE2V1 2xN4GlycoAsn-LY96 TLR1 p-IRAK2 UBC(533-608) TLR2 Triacyl lipopeptide TRAF6 p-PELI2 TLR6 p-Pellino-1,2,(3)GPIN-CD14(20-345) 2xN4GlycoAsn-TLR4 LPS CD14(20-345) CD14(20-345) Major outer membrane protein P IRAK2 PI(4,5)P2 Major outer membrane protein P GPIN-CD14(20-345) PI(4,5)P2 GPIN-CD14(20-345) PI(4,5)P2 2xN4GlycoAsn-LY96 ADPGPIN-CD14(20-345) TRAF6:hp-IRAK1:PellinoBTK 2xN4GlycoAsn-TLR4 2xN4GlycoAsn-TLR4 GPIN-CD14(20-345) LPS TAB2 Clostridial peptidoglycan GPIN-CD14(20-345) TLR6 TAB3 2xN4GlycoAsn-LY96 LPS p-T342,T345,S346-IRAK4 4xPalmC-CD36 TRAF6:hp-IRAK1p-4Y-TIRAP LPS 2xN4GlycoAsn-TLR4 2xN4GlycoAsn-TLR4 CD14(20-345) LPS p-4Y-TIRAP p-T342,T345,S346-IRAK4 MAP3K7 ADPTLR1 2xN4GlycoAsn-TLR4 TIRAP LPS MAP3K1 TAK1 activates NFkBby phosphorylationand activation ofIKKs complex4xPalmC-CD36 Diacyl lipopeptide Triacyl lipopeptide IRAK1, IRAK2TLR2 TIRAPMYD88 4xPalmC-CD36 Diacyl lipopeptide LPS Clostridial peptidoglycan Lipoteichoic acid PI(4,5)P2 p-4Y-TIRAP pp-IRAK1:p-IRAK4:oligo-MyD88:TIRAP:activated TLRK63polyUb Diacyl lipopeptide p-IRAK1:p-IRAK4:oligo-MyD88:TIRAP:activated TLRp-2S,S376,T,T209,T387-IRAK1 Major outer membrane protein P p-T342,T345,S346-IRAK4 CHUK PI(4,5)P2 TLR6 CD14(20-345) Major outer membrane protein P Triacyl lipopeptide MYD88 2xN4GlycoAsn-TLR4 p-4Y-TIRAP Diacyl lipopeptide IRAK2:p-S,2T-IRAK4:oligo-MyD88:Mal:activated TLRTriacyl lipopeptide TAB2 2xN4GlycoAsn-LY96 K63polyUb-TRAF6 MAP3K7 TRAF6:hp-IRAK1:p-IRAK4:oligo-MyD88:TIRAP:activated TLRSIGIRRIRAK1 MYD88 K63polyUbDiacyl lipopeptide UBE2N:UBE2V1Clostridial peptidoglycan TRAF6ATPDiacyl lipopeptide GPIN-CD14(20-345) Clostridial peptidoglycan PI(4,5)P2 MEKK1:activatedTRAF6p-PELI3 TLR1 TRAF6 2xN4GlycoAsn-TLR4 p-Pellino:hp-IRAK1:TRAF6ADPGPIN-CD14(20-345) p-4Y-TIRAP Major outer membrane protein P p-T209-IRAK1 Clostridial peptidoglycan TRAF6 2xN4GlycoAsn-LY96 GPIN-CD14(20-345) TAB2 p-PELI3 TLR2 2xN4GlycoAsn-LY96 K63polyUb-TRAF6 TLR1 Clostridial peptidoglycan p-T342,T345,S346-IRAK4 CD14(20-345) 2xN4GlycoAsn-TLR4 Diacyl lipopeptide TLR2 Triacyl lipopeptide ADP2xN4GlycoAsn-LY96 BTK 4xPalmC-CD36 p-IRAK2 Lipoteichoic acid 2xN4GlycoAsn-LY96 UBB(1-76) TLR6 PI(4,5)P2 BTK Diacyl lipopeptide UBE2N p-T342,T345,S346-IRAK4 ADPp-4Y-TIRAP MAP kinaseactivationPI(4,5)P2 CD14(20-345) LPS 464619, 2078461946788126, 60463, 29, 58, 794656243814655, 56, 66, 706346464646561919, 207, 12, 24, 5819, 204629, 521929, 52198129, 523629, 5281191919, 20468119, 204619, 201147, 75, 764619463646461919, 2019, 208146191981198128, 33, 371956, 701981461963198181468126, 5381814619, 2019, 204619, 20461927, 684646468178463, 793, 1139, 44, 57, 8046364619, 208119, 208119, 20464619, 2019, 20193, 1119, 20464610, 127, 12, 21, 24, 58


The first known downstream component of TLR4 and TLR2 signaling is the adaptor MyD88. Another adapter MyD88-adaptor-like (Mal; also known as TIR-domain-containing adaptor protein or TIRAP) has also been described for TLR4 and TLR2 signaling. MyD88 comprises an N-terminal Death Domain (DD) and a C-terminal TIR, whereas Mal lacks the DD. The TIR homotypic interactions bring adapters into contact with the activated TLRs, whereas the DD modules recruit serine/threonine kinases such as interleukin-1-receptor-associated kinase (IRAK). Recruitment of these protein kinases is accompanied by phosphorylation, which in turn results in the interaction of IRAKs with TNF-receptor-associated factor 6 (TRAF6). The oligomerization of TRAF6 activates TAK1, a member of the MAP3-kinase family, and this leads to the activation of the IkB kinases. These kinases, in turn, phosphorylate IkB, leading to its proteolytic degradation and the translocation of NF-kB to the nucleus. Concomitantly, members of the activator protein-1 (AP-1) transcription factor family, Jun and Fos, are activated, and both AP-1 transcription factors and NF-kB are required for cytokine production, which in turn produces downstream inflammatory effects. View original pathway at:Reactome.


Pathway is converted from Reactome ID: 166058
Reactome version: 66
Reactome Author 
Reactome Author: de Bono, Bernard

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