You are viewing an incomplete version of our website. Please click to reload the website as full version.

TLR Signaling

As part of the innate immune system the Toll-like receptor (TLR) signaling pathway contributes to the first line of defense against microbial pathogens. The innate immune system was historically considered nonspecific in response to different invading pathogens, targeting a wide array of pathogenic organisms, including viruses, bacteria, and fungi. This paradigm substantially shifted with the discovery of the Toll receptor in Drosophila.

To date, 10 members of the family have been identified in human and 13 in mouse. Homologs have also been discovered in plants, illustrating the high-degree of conservation in this receptor class.

Different TLRs recognize specific pathogen-associated molecular patterns (PAMPs). The chemical nature of these PAMPs is highly diverse; e.g. lipopolysaccharide (LPS) of gram-negative bacteria are recognized by TLR4 while TLR5 recognizes the bacterial protein flagellin. Ligands for TLR3, 7, 8, and 9 are nucleic acids, and TLR2 is specific for lipoproteins.

Binding of a TLR ligand to the N-terminal ectodomain of a TLR prompts the formation of TLR homo- or heterodimers. Following dimerization, TLR signals are transduced via a cytoplasmic C-terminal Toll IL-1 receptor (TIR) domain to a set of adapter proteins.

Downstream, TLR signaling engages two distinct pathways in which either TRIF (TICAM2) or MyD88 are the key component. Both pathways culminate in the induction of inflammatory cytokines (TNF, IL-6, IL-12), type I interferons (IFN-alpha, IFN-beta), or apoptosis. Furthermore, TLR signaling induces dendritic cell maturation and contributes consequently to the adaptive immune response.

Download pathway image as PDF

Toll-Like Receptors

TLR4 (Toll-Like Receptor 4):

The protein encoded by this gene is a member of the Toll-like receptor (TLR) family which plays a fundamental role in pathogen recognition and activation of innate immunity. TLRs are highly conserved from Drosophila to humans and share structural and functional similarities. They recognize pathogen-associated molecular patterns that are expressed on infectious agents, and mediate the production...   More...

TLR2 - Toll-Like Receptor 2

The protein encoded by this gene is a member of the Toll-like receptor (TLR) family which plays a fundamental role in pathogen recognition and...

TLR3 - Toll-Like Receptor 3

The protein encoded by this gene is a member of the Toll-like receptor (TLR) family which plays a fundamental role in pathogen recognition and...
Antigens in this category:
TLR1 - Toll-Like Receptor 1: TLR1 antibodies TLR1 ELISA Kits TLR1 Proteins
TLR5 - Toll-Like Receptor 5: TLR5 antibodies TLR5 ELISA Kits TLR5 Proteins
TLR6 - Toll-Like Receptor 6: TLR6 antibodies TLR6 ELISA Kits TLR6 Proteins
TLR7 - Toll-Like Receptor 7: TLR7 antibodies TLR7 ELISA Kits TLR7 Proteins
TLR8 - Toll-Like Receptor 8: TLR8 antibodies TLR8 ELISA Kits TLR8 Proteins
TLR9 - Toll-Like Receptor 9: TLR9 antibodies TLR9 ELISA Kits TLR9 Proteins
TLR10 - Toll-Like Receptor 10: TLR10 antibodies TLR10 ELISA Kits TLR10 Proteins

Coreceptors

LY96 - Lymphocyte Antigen 96

This gene encodes a protein which associates with toll-like receptor 4 on the cell surface and confers responsiveness to lipopolysaccyaride (LPS),...

CD36 (CD36 Molecule (thrombospondin Receptor)):

The protein encoded by this gene is the fourth major glycoprotein of the platelet surface and serves as a receptor for thrombospondin in platelets...
Antigens in this category:
UNC93B1 - Unc-93 Homolog B1 (C. Elegans): UNC93B1 antibodies UNC93B1 ELISA Kits  
CD14 (CD14 Molecule): CD14 antibodies CD14 ELISA Kits CD14 Proteins
LBP (Lipopolysaccharide Binding Protein): LBP antibodies LBP ELISA Kits LBP Proteins

Adapters

MYD88 (Myeloid Differentiation Primary Response Gene (88)):

This gene encodes a cytosolic adapter protein that plays a central role in the innate and adaptive immune response. This protein functions as an essential signal transducer in the interleukin-1 and Toll-like receptor signaling pathways. These pathways regulate that activation of numerous proinflammatory genes. The encoded protein consists of an N-terminal death domain and a C-terminal...   More...

TICAM2 (MIM 147810) (TIR) domain-containing adaptor protein involved in Toll receptor signaling (see TLR4\):

TIRP is a Toll/interleukin-1 receptor (IL1R\; MIM 147810) (TIR) domain-containing adaptor protein involved in Toll receptor signaling (see TLR4\; MIM 603030).[supplied by OMIM, Apr 2004].   More...
Antigens in this category:
TIRAP (Toll-Interleukin 1 Receptor (TIR) Domain Containing Adaptor Protein): TIRAP antibodies TIRAP ELISA Kits TIRAP Proteins
TICAM1 (Toll-Like Receptor Adaptor Molecule 1): TICAM1 antibodies TICAM1 ELISA Kits TICAM1 Proteins

Inhibitors

IRAK3 (Interleukin-1 Receptor-Associated Kinase 3):

This gene encodes a member of the interleukin-1 receptor-associated kinase protein family. Members of this family are essential components of the Toll/IL-R immune signal transduction pathways. This protein is primarily expressed in monocytes and macrophages and functions as a negative regulator of Toll-like receptor signaling. Mutations in this gene are associated with a susceptibility to...   More...
Antigens in this category:
SOCS1 (Suppressor of Cytokine Signaling 1): SOCS1 antibodies SOCS1 ELISA Kits SOCS1 Proteins
TNFAIP3 - Tumor Necrosis Factor, alpha-Induced Protein 3: TNFAIP3 antibodies TNFAIP3 ELISA Kits TNFAIP3 Proteins
TAX1BP1 (Tax1 (Human T-Cell Leukemia Virus Type I) Binding Protein 1): TAX1BP1 antibodies TAX1BP1 ELISA Kits TAX1BP1 Proteins
TANK (TRAF Family Member-Associated NFKB Activator): TANK antibodies TANK ELISA Kits TANK Proteins
PTPN1 (Protein tyrosine Phosphatase, Non-Receptor Type 1): PTPN1 antibodies PTPN1 ELISA Kits PTPN1 Proteins
PTPN6 (Protein-tyrosine Phosphatase 1C): PTPN6 antibodies PTPN6 ELISA Kits PTPN6 Proteins
SARM1 (Sterile alpha and TIR Motif Containing 1): SARM1 antibodies   SARM1 Proteins

Transducer

IRAK4 (Interleukin-1 Receptor-Associated Kinase 4):

This gene encodes a kinase that activates NF-kappaB in both the Toll-like receptor (TLR) and T-cell receptor (TCR) signaling pathways. The protein is essential for most innate immune responses. Mutations in this gene result in IRAK4 deficiency and recurrent invasive pneumococcal disease. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq,...   More...

TRAF3 (TNF Receptor-Associated Factor 3):

The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins associate with, and mediate...

TRAF6 (TNF Receptor-Associated Factor 6):

The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins are associated with, and...
Antigens in this category:
TBK1 - TANK-Binding Kinase 1: TBK1 antibodies TBK1 ELISA Kits TBK1 Proteins
IRAK1 (Interleukin-1 Receptor-Associated Kinase 1): IRAK1 antibodies IRAK1 ELISA Kits IRAK1 Proteins
IRAK2 (Interleukin-1 Receptor-Associated Kinase 2): IRAK2 antibodies IRAK2 ELISA Kits IRAK2 Proteins
IKBKE - Inhibitor of kappa Light Polypeptide Gene Enhancer in B-Cells, Kinase epsilon: IKBKE antibodies IKBKE ELISA Kits IKBKE Proteins
RIPK1 (Receptor (TNFRSF)-Interacting serine-threonine Kinase 1): RIPK1 antibodies RIPK1 ELISA Kits RIPK1 Proteins
TAB1 - TGF-beta Activated Kinase 1/MAP3K7 Binding Protein 1: TAB1 antibodies TAB1 ELISA Kits TAB1 Proteins
TAB2 - TGF-beta Activated Kinase 1/MAP3K7 Binding Protein 2: TAB2 antibodies TAB2 ELISA Kits TAB2 Proteins
TAB3 - TGF-beta Activated Kinase 1/MAP3K7 Binding Protein 3: TAB3 antibodies TAB3 ELISA Kits TAB3 Proteins
ECSIT - ECSIT Homolog (Drosophila): ECSIT antibodies   ECSIT Proteins

NF-kappaB

Antigens in this category:
CHUK (conserved Helix-Loop-Helix Ubiquitous Kinase): CHUK antibodies CHUK ELISA Kits CHUK Proteins
IKBKB (Inhibitor of kappa Light Polypeptide Gene Enhancer in B-Cells, Kinase beta): IKBKB antibodies IKBKB ELISA Kits IKBKB Proteins
IKBKG (Inhibitor of kappa Light Polypeptide Gene Enhancer in B-Cells, Kinase gamma): IKBKG antibodies IKBKG ELISA Kits IKBKG Proteins
NFKB1 (Nuclear Factor of kappa Light Polypeptide Gene Enhancer in B-Cells 1): NFKB1 antibodies NFKB1 ELISA Kits NFKB1 Proteins
NFkBP65 - p65: NFkBP65 antibodies NFkBP65 ELISA Kits NFkBP65 Proteins
NFKBIA (Nuclear Factor of kappa Light Polypeptide Gene Enhancer in B-Cells Inhibitor, alpha): NFKBIA antibodies NFKBIA ELISA Kits NFKBIA Proteins

Mitogen Activated Protein Kinases

Antigens in this category:
MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1): MAP3K1 antibodies MAP3K1 ELISA Kits MAP3K1 Proteins
MAP3K7 (Mitogen-Activated Protein Kinase Kinase Kinase 7): MAP3K7 antibodies MAP3K7 ELISA Kits MAP3K7 Proteins
MAP2K3 (Mitogen-Activated Protein Kinase Kinase 3): MAP2K3 antibodies MAP2K3 ELISA Kits MAP2K3 Proteins
MAP2K4 (Mitogen-Activated Protein Kinase Kinase 4): MAP2K4 antibodies MAP2K4 ELISA Kits MAP2K4 Proteins
MAP2K6 (Mitogen-Activated Protein Kinase Kinase 6): MAP2K6 antibodies MAP2K6 ELISA Kits MAP2K6 Proteins
MAP2K7 (Mitogen-Activated Protein Kinase Kinase 7): MAP2K7 antibodies MAP2K7 ELISA Kits MAP2K7 Proteins
CREB1 (CAMP Responsive Element Binding Protein 1): CREB1 antibodies CREB1 ELISA Kits CREB1 Proteins
MAPK8 - JNK: MAPK8 antibodies MAPK8 ELISA Kits MAPK8 Proteins
MAPK9 (Mitogen-Activated Protein Kinase 9): MAPK9 antibodies MAPK9 ELISA Kits MAPK9 Proteins
MAPK10 (Mitogen-Activated Protein Kinase 10): MAPK10 antibodies MAPK10 ELISA Kits MAPK10 Proteins

Interferon Regulatory Factors

IRF7 - Interferon Regulatory Factor 7

IRF7 encodes interferon regulatory factor 7, a member of the interferon regulatory transcription factor (IRF) family. IRF7 has been shown to play a role in the transcriptional activation of virus-inducible cellular genes, including interferon beta chain genes. Inducible expression of IRF7 is largely restricted to lymphoid tissue. Multiple IRF7 transcript variants have been identified, although...   More...

IRF3 - Interferon Regulatory Factor 3

This gene encodes a member of the interferon regulatory transcription factor (IRF) family. The encoded protein is found in an inactive cytoplasmic...

IRF5 - Interferon Regulatory Factor 5

This gene encodes a member of the interferon regulatory factor (IRF) family, a group of transcription factors with diverse roles, including...

Cell Survival

Antigens in this category:
PIK3CA (Phosphoinositide-3-Kinase, Catalytic, alpha Polypeptide): PIK3CA antibodies PIK3CA ELISA Kits PIK3CA Proteins
PIK3CG (Phosphoinositide-3-Kinase, Catalytic, gamma Polypeptide): PIK3CG antibodies PIK3CG ELISA Kits PIK3CG Proteins
AKT1 - AKT: AKT1 antibodies AKT1 ELISA Kits AKT1 Proteins
AKT2 (V-Akt Murine Thymoma Viral Oncogene Homolog 2): AKT2 antibodies AKT2 ELISA Kits AKT2 Proteins
AKT3 (V-Akt Murine Thymoma Viral Oncogene Homolog 3 (Protein Kinase B, Gamma)): AKT3 antibodies AKT3 ELISA Kits AKT3 Proteins

Apoptosis

Antigens in this category:
FADD (Fas (TNFRSF6)-Associated Via Death Domain): FADD antibodies FADD ELISA Kits FADD Proteins
CASP8 - Caspase 8: CASP8 antibodies CASP8 ELISA Kits CASP8 Proteins