Activated TLR2/4:TIRAP interacts with BTK

Stable Identifier
R-HSA-2559414
Type
Reaction [binding]
Species
Homo sapiens
Related Species
Neisseria meningitidis serogroup B, Chlamydia trachomatis
Compartment
Synonyms
Activated TLR2/4:MAL interacts with BTK
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

Bruton's tyrosine kinase (BTK) is a cytoplasmic protein tyrosine kinase, which plays an essential role in B cell receptor (BCR) signaling (Brunner C et al. 2005). BTK has been also implicated in TLR signaling (Lee KG et al. 2012, Jefferies CA et al. 2003; Doyle SL et al. 2007). Interaction studies revealed that BTK can associate with intracellular TIR-domains of TLRs 4, 6, 8 and 9. Furthermore, BTK was found to interact with other proteins involved in TLR2/4 signaling - MyD88, MAL and IRAK-1 (Jefferies CA et al. 2003)

Loss of BTK function causes X-linked agammaglobulinemia (XLA), a rare primary immunode?ciency disease with severe defects in early B-cell development resulting in an almost complete absence of peripheral B cells and severely reduced serum levels of immunoglobulins of all classes (Väliaho J et al. 2006). Affected individuals suffer from recurrent bacterial and enteroviral infections. It remains unclear whether XLA patients have normal or impared TLR signaling functions. LPS-stimulated monocytes from XLA patients were found to produce reduced amounts of TNFalpha (Horwood NJ et al. 2003), These data contradict a study that showed enhanced amounts of TNFalpha and IL6 comparing to control cells, starting at 6 hours and extending for 48 hours (Marron TU et al. 2012). The other group reported similar expression TNFalpha upon TLR4 triggering, compared with healthy control cells (Perez de Diego R et al. 2006). Thus, the effect of BTK deficiency on TLR-mediated inflammation needs to be further clarified.

Literature References
PubMed ID Title Journal Year
22454496 Bruton's tyrosine kinase phosphorylates Toll-like receptor 3 to initiate antiviral response

Lee, KG, Xu, S, Kang, ZH, Huo, J, Huang, M, Liu, D, Takeuchi, O, Akira, S, Lam, KP

Proc Natl Acad Sci U S A 2012
12724322 Bruton's tyrosine kinase is a Toll/interleukin-1 receptor domain-binding protein that participates in nuclear factor kappaB activation by Toll-like receptor 4

Jefferies, CA, Doyle, S, Brunner, C, Dunne, A, Brint, E, Wietek, C, Walch, E, Wirth, T, O'Neill, LA

J Biol Chem 2003
15944945 Bruton's Tyrosine Kinase is involved in innate and adaptive immunity

Brunner, C, Müller, B, Wirth, T

Histol Histopathol 2005
Participants
Participant Of
Authored
Reviewed
Created