SARM binds viral dsRNA:TLR3:TICAM1

Stable Identifier
R-HSA-9014320
Type
Reaction [binding]
Species
Homo sapiens
Related Species
Rotavirus, Influenza A virus, Hepatitis B virus, Hepatitis C Virus, Human herpesvirus 1
Compartment
Synonyms
Negative regulator SARM binds to TRIF within activated TLR3 complex
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

SARM (sterile alpha-and armadillo-motif-containing protein) is a TIR-domain-containing adaptor, which functions as a negative regulator of TRIF (TICAM1)-dependent Toll-like receptor signaling in humans. A pairwise yeast two-hybrid assay demonstrated that SARM is capable of binding directly to TICAM1 (Carty M et al. 2006). GST pulldown studies suggest that protein-protein interactions occur between the TIR domains of SARM and TICAM1 (Carlsson E et al. 2016). The complex of TICAM1:SARM is thought to inhibit downstream TRIF signaling by preventing the recruitment of TRIF effector proteins (Carty M et al. 2006).

SARM expression was shown to inhibit poly(I:C)-induced TICAM1-dependent NFkappaB activaion, RANTES production and IRF activation in human embryonic kidney HEK293 cells (Carty M et al. 2006). Moreover, suppression of endogenous SARM expression by siRNA led to enhanced TLR3- and TLR4-dependent gene induction in both transformed HEK293 and primary PBMC cells (Carty M et al. 2006), Thus, SARM associates with TICAM1 via its TIR and sterile-alpha motif (SAM) domains to block the induction of proinflammatory genes downstream TLR3.

Literature References
PubMed ID Title Journal Year
16964262 The human adaptor SARM negatively regulates adaptor protein TRIF-dependent Toll-like receptor signaling

Carty, M, Goodbody, R, Schröder, M, Stack, J, Moynagh, PN, Bowie, AG

Nat. Immunol. 2006
Participants
Participant Of
Event Information
Authored
Reviewed
Created