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

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2519, 24, 76, 7814, 4672, 7320, 26, 47, 6122, 23, 493762, 64, 71, 8129, 30, 44, 53136620, 45, 613737, 3829, 30, 44, 5321, 23, 49, 794, 15, 17, 34, 35, 54...37, 488, 47, 5531, 36, 751, 7, 6551, 741, 28, 43, 48, 65...37, 38763931, 40, 5913, 32, 38, 52, 63...cytosolp-IRAK2 CD14(20-345) TAB2 Major outer membrane protein P p-T209-IRAK1 TRAF6:hp-IRAK1:p-IRAK4:oligo-MyD88:TIRAP:activated TLRIRAK2:p-S,2T-IRAK4:oligo-MyD88:Mal:activated TLR4xPalmC-CD36 TLR6 Diacyl lipopeptide TAB1 mip p-PELI3 TLR1 IRAK1/orIRAK2:p-IRAK4:MyD88oligomer:TIRAP:activated TLRATPTIRAP:PI(4,5)P2:activated TLR2/4Lipoteichoic acid TIRAP:PI(4,5)P2Clostridial peptidoglycan mip Lipoteichoic acid Triacyl lipopeptide TLR2 TLR1 Diacyl lipopeptide p-PELI3 UBB(77-152) BTKLPS Diacyl lipopeptide Clostridial peptidoglycan Lipoteichoic acid Major outer membrane protein P p-2S,S376,T,T209,T387-IRAK1 MAP3K7 Activated TLR1:2 orTLR 2:6heterodimers orTLR4 homodimerLPS IKBKG MYD88 Lipoteichoic acid TRAF6:p-IRAK2MYD88 K63polyUb-TRAF6 LPS Diacyl lipopeptide p-2S,S376,T,T209,T387-IRAK1 MAP3K1GPIN-CD14(20-345) PI(4,5)P2 MYD88 2xN4GlycoAsn-LY96 GPIN-CD14(20-345) TLR2 ECSITp-PELI2 UBB(1-76) Major outer membrane protein P 2xN4GlycoAsn-LY96 Lipoteichoic acid ADPTLR6 Lipoteichoic acid BTK Diacyl lipopeptide p-PELI2 2xN4GlycoAsn-TLR4 TRAF6:K63-linkedpolyUb p-IRAK1:IKKcomplexp-T342,T345,S346-IRAK4 Clostridial peptidoglycan TRAF6 Triacyl lipopeptide 2xN4GlycoAsn-LY96 Diacyl lipopeptide CD14(20-345) LPS TLR6 p-4Y-TIRAP K63polyUb-hp-IRAK1 LPS GPIN-CD14(20-345) ADPTLR6 2xN4GlycoAsn-TLR4 PI(4,5)P2 TLR2 IRAK3Lipoteichoic acid Major outer membrane protein P GPIN-CD14(20-345) MYD88 Triacyl lipopeptide Clostridial peptidoglycan Clostridial peptidoglycan pp-IRAK1:p-IRAK4:oligo-MyD88:TIRAP:activated TLRMajor outer membrane protein P TRAF6Lipoteichoic acid ATP2xN4GlycoAsn-LY96 GPIN-CD14(20-345) p-IRAK2 p-T342,T345,S346-IRAK4 p-IRAK2:K63-linkedpUboligo-TRAF6:freeK63-linkedpUb:p-TAK1complexLPS mip 4xPalmC-CD36 RPS27A(1-76) PI(4,5)P2 p-IRAK2 IKBKB MYD88 Triacyl lipopeptide Clostridial peptidoglycan LPS p-PELI2 GPIN-CD14(20-345) PI(4,5)P2 IRAK2 Lipoteichoic acid ADPATPK63-linked polyUbp-IRAK1:TRAF6CD14(20-345) TLR1 2xN4GlycoAsn-LY96 LPS Major outer membrane protein P Major outer membrane protein P GPIN-CD14(20-345) CD14(20-345) GPIN-CD14(20-345) p-S,2T-IRAK4:oligo-MyD88:TIRAP:activated TLR receptorTLR6 UBC(1-76) p-IRAK2 MyD88:TIRAP:BTK:activated TLR2/4p-T184,T187-MAP3K7 2xN4GlycoAsn-LY96 BTK CHUK mip TLR2 CD14(20-345) TAB1 p-4Y-TIRAP CD14(20-345) TLR6 K63polyUb TLR1 BTK CD14(20-345) TLR6 PI(4,5)P2 p-4Y-TIRAP TLR1 K63polyUb-TRAF6 IRAK2 TRAF6:hp-IRAK1TLR6 Diacyl lipopeptide UBE2N:UBE2V1CD14(20-345) TLR2 Clostridial peptidoglycan UBC(77-152) Triacyl lipopeptide p-PELI1 UBC(305-380) LPS TLR2 TLR2 mip BTK CD14(20-345) GPIN-CD14(20-345) TLR1 mip TRAF6:p-IRAK2:p-IRAK4:oligo-MyD88:TIRAP:activated TLRSIGIRRBTK TLR2 PI(4,5)P2 K63polyUb-hp-IRAK1 mip IKBKG p-IRAK2:K63-linkedpUb oligo-TRAF6mip 4xPalmC-CD36 TLR6 2xN4GlycoAsn-LY96 TLR2 2xN4GlycoAsn-LY96 GPIN-CD14(20-345) PI(4,5)P2 GPIN-CD14(20-345) Clostridial peptidoglycan TLR1 p-IRAK2 K63polyUbGPIN-CD14(20-345) Lipoteichoic acid ATPp-PELI1 IRAK4PI(4,5)P2IRAK1:p-S,2T-IRAK4:oligo-MyD88:TIRAP:activated TLR4xPalmC-CD36 PI(4,5)P2 2xN4GlycoAsn-LY96 PI(4,5)P2 Triacyl lipopeptide TLR1 TRAF6Lipoteichoic acid MYD88 mip 4xPalmC-CD36 BTK UBE2N TRAF6 TLR1 Major outer membrane protein P PI(4,5)P2 K63polyUbCD14(20-345) Triacyl lipopeptide TAB3 TLR6 TRAF6 2xN4GlycoAsn-LY96 2xN4GlycoAsn-TLR4 TLR1 MAP3K1 Triacyl lipopeptide PI(4,5)P2 4xPalmC-CD36 Lipoteichoic acid p-4Y-TIRAP p-4Y-TIRAP Lipoteichoic acid IRAK4 CD14(20-345) Major outer membrane protein P TIRAP Clostridial peptidoglycan PI(4,5)P2 CD14(20-345) IRAK2 p-IRAK1:p-IRAK4:oligo-MyD88:TIRAP:activated TLR2xN4GlycoAsn-TLR4 mip ADPBTK TLR1 IRAK1 p-4Y-TIRAP oligo-MyD88:TIRAP:BTK:activated TLR4xPalmC-CD36 CD14(20-345) PI(4,5)P2 MAP kinaseactivationTLR2 p-2S,S376,T,T209,T387-IRAK1 p-T342,T345,S346-IRAK4 Clostridial peptidoglycan TRAF6 2xN4GlycoAsn-TLR4 p-T342,T345,S346-IRAK4 ADPTLR2 TAB1 CD14(20-345) PI(4,5)P2 2xN4GlycoAsn-LY96 TLR6 LPS LPS mip TLR6 Clostridial peptidoglycan p-2S,S376,T,T209,T387-IRAK1 BTK Diacyl lipopeptide TRAF6 2xN4GlycoAsn-TLR4 ATPp-4Y-TIRAP 4xPalmC-CD36 LPS Lipoteichoic acid TAK1 activates NFkBby phosphorylationand activation ofIKKs complexK63polyUb-TRAF6 GPIN-CD14(20-345) IRAK4 BTK TRAF6 UBC(457-532) TLR2 TLR2 2xN4GlycoAsn-LY96 LPS Clostridial peptidoglycan BTK 4xPalmC-CD36 PI(4,5)P2 TRAF6 TLR6 PI(4,5)P2 Triacyl lipopeptide Diacyl lipopeptide ADPDiacyl lipopeptide TLR1 TLR1 GPIN-CD14(20-345) Diacyl lipopeptide p-4Y-TIRAP TIRAP:PI(4,5)P2:BTK:activated TLR2/4TLR6 Triacyl lipopeptide ATPTriacyl lipopeptide TRAF6 mip TAB2 MAP3K7 p-T342,T345,S346-IRAK4 TLR2 p-PELI1 TRAF6 Diacyl lipopeptide mip p-4Y-TIRAP TAK1 complexUBC(229-304) Diacyl lipopeptide TRAF6 p-Pellino:hp-IRAK1:TRAF6p-PELI3 TLR2 p-Pellino-1,2,(3)p-4Y-TIRAP 2xN4GlycoAsn-TLR4 UBC(533-608) MEKK1:activatedTRAF6MYD88 TLR1 Major outer membrane protein P Lipoteichoic acid TRAF6Ub2xN4GlycoAsn-LY96 mip 2xN4GlycoAsn-TLR4 2xN4GlycoAsn-TLR4 Clostridial peptidoglycan UBC(381-456) 4xPalmC-CD36 UBB(153-228) UBE2V1 Major outer membrane protein P mip Major outer membrane protein P 4xPalmC-CD36 p-4Y-TIRAP p-IRAK2:K63-linkedpUboligo-TRAF6:freeK63 pUb:TAK1complexp-T342,T345,S346-IRAK4 TAB3 Triacyl lipopeptide IKBKB LPS CD14(20-345) BTK UBA52(1-76) 2xN4GlycoAsn-TLR4 2xN4GlycoAsn-LY96 2xN4GlycoAsn-TLR4 TLR2 SOCS1TLR2 CHUK:IKBKB:IKBKGMajor outer membrane protein P PI(4,5)P2 ATP2xN4GlycoAsn-LY96 p-3S,3T-IRAK1:p-S,2T-IRAK4:oligo-MyD88:TIRAP:activated TLRADPClostridial peptidoglycan 4xPalmC-CD36 2xN4GlycoAsn-LY96 p-T342,T345,S346-IRAK4 mip Major outer membrane protein P TAB3 p-4Y-TIRAP Clostridial peptidoglycan p-IRAK2 Clostridial peptidoglycan p-IRAK2:p-IRAK4:oligo-MyD88:TIRAP:activated TLRp-4Y-TIRAP MYD88 BTK 2xN4GlycoAsn-TLR4 UBC(609-684) LPS p-IRAK2:oligo-TRAF6BTK Triacyl lipopeptide Triacyl lipopeptide Triacyl lipopeptide Diacyl lipopeptide p-T342,T345,S346-IRAK4 2xN4GlycoAsn-LY96 TLR6 MYD88 LPS Diacyl lipopeptide 2xN4GlycoAsn-TLR4 p-T209,T387-IRAK1 mip GPIN-CD14(20-345) IRAK1 GPIN-CD14(20-345) TLR1 TLR6 Triacyl lipopeptide CD14(20-345) BTK ADP4xPalmC-CD36 LPS Triacyl lipopeptide TAB2 GPIN-CD14(20-345) p-4Y-TIRAP 4xPalmC-CD36 MYD88 Major outer membrane protein P 4xPalmC-CD36 Clostridial peptidoglycan TLR1 Diacyl lipopeptide CD14(20-345) MYD88MYD88 2xN4GlycoAsn-TLR4 TIRAPIRAK1, IRAK2Lipoteichoic acid TLR1 TLR6 BTK 2xN4GlycoAsn-TLR4 2xN4GlycoAsn-TLR4 p-IRAK2 TIRAP UBC(153-228) MYD88 4xPalmC-CD36 K63polyUb TIRAP ATPLipoteichoic acid p-T342,T345,S346-IRAK4 Diacyl lipopeptide 2xN4GlycoAsn-TLR4 IRAK1 Major outer membrane protein P p-2S,S376,T,T209,T387-IRAK1 activatedTLR2/4:p-4Y-TIRAP:PI(4,5)P2:BTKCHUK IRAK4:oligo-MyD88:TIRAP:activated TLRMajor outer membrane protein P 4xPalmC-CD36 MYD88 TRAF6:hp-IRAK1:Pellino11, 691111, 693393394533911, 69933333310, 651, 6511, 6933333327, 70333311112, 37, 809918, 21, 47, 56116193311, 69333333114511335, 60911, 6933913, 773316, 486147, 56114739111911, 6911, 69333345336, 12, 41, 67393311114011, 6911, 6933395, 5711, 6911911, 69113, 42, 503327, 40, 64, 79331110, 64, 65911, 69911, 693311, 6994733333316, 48111, 6511, 6993327, 31, 40, 64, 79111116, 486533


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: 75
Reactome Author 
Reactome Author: de Bono, Bernard

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