MAL:BTK:activated TLR2/4 activated TLR2/4:p-4Y-MAL:BTK MAL is phosphorylated by BTK Authored: Shamovsky, V, 2012-04-19 EC Number: 2.7.10 Edited: Shamovsky, V, 2012-11-06 MAL(TIRAP) undergoes tyrosine phosphorylation mediated by Bruton's tyrosine kinase (BTK). BTK-specific inhibitor, LFM-A13, blocked the phosphorylation of MAL in human HEK293 stimulated with LPS or macrophage-activating lipopeptide-2. LFM-A13 also inhibited activation of NF-kB in LPS-treated human monocytic cell line THP-1 [Gray P et al 2006; Jefferies CA et al 2003]. Tyr-86, Tyr-106 and Tyr-187 were identified as possible phosphorylation sites [Gray P et al 2006]. An additional study has shown that Tyr-86, Tyr-106, and Tyr-159 are important residues, as mutagenesis of these residues impaired MAL phosphorylation, affected its interaction with BTK and also impaired downstream signaling [Piao W et al 2008]. Pubmed12724322 Pubmed16439361 Pubmed18070880 Reactome Database ID Release 432201322 Reactome, http://www.reactome.org ReactomeREACT_120882 Reviewed: D'Eustachio, P, 2012-05-25 Reviewed: Napetschnig, Johanna, 2012-11-16