Toll-like Receptor(TLR) Signaling

Bacteria

Bacteria

Yeast

Zymosan

TIRAP

TIRAP

TRIF

MyD88

MyD88

FADD

IRAK4

TRAF6

TRAF6

RIP1

IRAK1

IRAK4

TAB1/2

TRAF6 IRAK1/2

PI3K

Rac1

Akt

IKK

Expression of Pro-inflammatory CytokinesApoptosis Expression of Type I Interferon

IκB

IKKε

ISRE

Casp-8

Caspase

Degradation

Cascade

TL

R2

TL

R1

TL

R5

TL

R5

dsRNA

ssRNA

CpG DNA

NAP1

TL

R4

CD

14

BLP/LAM/PGN Flagellin LPS

MD-2

TRIF

TL

R4

TRAF3TAK1

TL

R6

TL

R2

CD

14

ERK

Bacteria Bacteria

Cell Membrane

Nuclear Membrane

Nucleus

IRF5 IRF7 IRF3

TBK1

TLR3

TANK

TLR7

TLR8

TLR9

TLR3

TRAMTIRAP

MyD88

MyD88

MyD88

MyD88

MKKsIKKs

p38JNK

NF-�B IRF7IRF5c-Jun IRF3

I�B�

NF-�B

ISRE ISRE

Toll-like receptors (TLRs) are membrane-bound receptors identified as homologs of Toll in Drosophila. TLRs play crucial

roles in the innate immune system by recognizing various ligands of pathogen-associated molecular patterns (PAMPs, e.g.

dsRNA) derived from various microbes or damage-associated molecular patterns (DAMPs) derived from damaged cell

contents (not shown). TLRs localize to the cell surface or to intracellular compartments (e.g. endosome). Homo- or

heterodimer formation initiates signaling to the two major downstream adaptor proteins, MyD88 and TRIF. TIRAP conducts

the signal from TLR4 to MyD88, and TRAM mediates the signal from TLR4 to TRIF. TLR engagement induces formation of

the Myddosome, which is based on MyD88 and also contains IRAK1 and IRAK4. IRAK1 activation induces TRAF6 activation

following K63-linked polyubiquitination on TRAF6 itself and TAK1. TAK1 activation leads to the activation of IKK

complex-NF-kB and MAPKs (e.g. ERK, JNK, p38). MAPK activation leads to AP1 (e.g. c-jun) activation. TLR engagement

also induces TRIF activation following TRAF6 and TRAF3 recruitment. TRAF3 recruits TBK1 and IKKε for IRFs

phosphorylation and expression of interferon-β. Abbreviations: dsRNA, double-stranded RNA; ssRNA, single-stranded

RNA; BLP, Bacteria Lipoprotein; LAM, lipoarabinomannan; PGN, peptidoglycan; ISRE, Interferon-sensitive response

Key Products for TLR SignalingKey Products for TLR Signaling

Target Name Cat.No. Reactivity Applications Citations

TLR2

TLR4

TLR5

TLR7

TLR8

TLR9

IRAK1

Phospho-IRAK1 (Ser376)

Phospho-IRAK1 (Thr209)

Phospho-IRAK1 (Thr387)

IRAK4

Phospho-IRAK4 (Thr345)

Phospho-TAK1 (Thr184)

Phospho-TAK1 (Thr187)

Phospho-TAK1(Thr184 + Thr187)

IKK alpha + IKK beta

Phospho-IKK alpha/beta (Ser176 + Ser180)

JNK1+JNK2+JNK3

Phospho-JNK1 + 2 + 3 (Thr183+Tyr185)

p38 MAPK

Phospho-p38 MAPK (Thr180 + Tyr182)

AKT1+2+3

AKT

AKT

Phospho-AKT (Ser473)

ERK1 + ERK2

Phospho-ERK1/2 (Thr202 + Tyr204)

NFkB p65

Phospho-NFkB p65 (Ser536)

c-Jun

Phospho-c-Jun (Thr249)

Phospho-c-Jun (Thr91)

IRF3

IRF3

Phospho-IRF3 (Ser386)

Phospho-IRF3 (Ser396)

IRF7

Phospho-IRF7 (Ser471 + Ser472)

bs-1019R

bs-20595R

bs-1197R

bs-6601R

bs-8684R

bs-2717R

bs-28003R

bs-3192R

bs-20492R

bs-3194R

bs-2440R

bs-10208R

bs-3436R

bs-3438R

bs-3439R

bs-10123R

bs-3237R

bs-2592R

bs-1640R

bs-0637R

bs-0636R

bs-6951R

bsm-33278M

bsm-33282M

bs-0876R

bs-2637R

bs-3016R

bs-20355R

bs-0982R

bs-0670R

bs-5462R

bs-5458R

bs-2993R

bsm-52116R

bs-9278R

bs-3195R

bs-2994R

bs-3196R

Human,Mouse,Rat

Human,Mouse,Rat

Human,Mouse,Rat

Human,Mouse,Rat

Human,Mouse,Rat

Human,Mouse,Rat

Human,Mouse,Rat

Human,Mouse

Human

Human,Mouse,Rat

Human,Mouse,Rat

Human,Mouse,Rat

Human

Human,Mouse,Rat

Human,Mouse

Human,Mouse,Rat

Human,Mouse,Rat

Human,Mouse,Rat

Human,Mouse,Rat

Human,Mouse,Rat

Human,Mouse,Rat

Human,Mouse,Rat

Human

Human

Human,Mouse,Rat

Human,Mouse

Human,Mouse,Rat

Human,Mouse,Rat

Human,Mouse,Rat

Human,Mouse,Rat

Human

Human

Human,Mouse

Human,Mouse

Human,Mouse

Human,Mouse,Rat

Human,Mouse,Rat

Human,Mouse,Rat

WB,IHC-P

WB,FCM

WB

WB,IF

WB,IHC-P

WB,IHC-P,FCM

WB,IHC-P

WB,IHC-P,FCM

WB,IHC-P

WB,IHC-P,FCM

FCM

WB,IHC-P

WB

WB,IHC-P,FCM

WB

WB,IHC-P

WB,IHC-P

WB,IHC-P,FCM

WB,IHC-P,FCM

WB

WB

WB,FCM

WB

WB

WB,IHC-P

WB,IHC-P

WB,IHC-P,IF

WB,IHC-P,FCM

WB,IHC-P,FCM

WB,IHC-P,FCM

FCM

WB,FCM

WB

WB

WB,IHC-P,FCM

IHC-P,FCM

WB,IHC-P

WB,IHC-P,FCM

WB=Western Blot; IHC-P=Immunohistochemistry with Paraffin-Embedded Tissue Slides; IF=Immunofluorescence; FCM=Flow cytometry

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