Activated TLR2/4:TIRAP interacts with BTK

Stable Identifier
Reaction [binding]
Homo sapiens
Related Species
Chlamydia trachomatis, Neisseria meningitidis serogroup B
Activated TLR2/4:MAL interacts with BTK
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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
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

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

J Biol Chem 2003
22454496 Bruton's tyrosine kinase phosphorylates Toll-like receptor 3 to initiate antiviral response

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

Proc Natl Acad Sci U S A 2012
15944945 Bruton's Tyrosine Kinase is involved in innate and adaptive immunity

Müller, B, Brunner, C, Wirth, T

Histol Histopathol 2005
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