TASL is phosphorylated

Solute carrier family 15 member 4 protein (SLC15A4) and TLR adaptor interacting with SLC15A4 on the lysosome (TASL) control the activation of the key transcription factor IRF5 in response to endosomal Toll-like receptors (TLR7, TLR8, and TLR9) stimulation (Heinz L. et al., 2020). TASL is recruited to SLC15A4, located on the endolysosomal membrane (Heinz L. et al., 2020; Zhang H et al., 2023; Chen X et al., 2023; Boeszoermeny A et al., 2023). Activation of TASL likely involves phosphorylation at S294 as evidenced by a phosphomimetic S294D mutant (Heinz L. et al., 2020). While the precise kinase(s) phosphorylating TASL are yet to be fully elucidated, co-expression of TASL with TBK1, IKKε (IKBKE), or IKBKB kinases in human embryonic kidney 293 (HEK293) cells as well as knockout studies in human leukemia monocytic THP1 cells suggest involvement of IKBKB (IKKβ) (Heinz L. et al., 2020). SLC15A4-bound TASL recruits the transcription factor IRF5 leading to IRF5 phosphorylation and activation. <p>This Reactome events shows phosphorylation of TASL at S294.

载体蛋白家族15成员4蛋白（SLC15A4）及与溶酶体上的SLC15A4相互作用的TLR适配器（TASL）调控着关键转录因子IRF5在受到内体Toll样受体（TLR7、TLR8和TLR9）刺激后的激活反应（Heinz L. 等，2020年）。TASL被招募至位于内质溶酶体膜上的SLC15A4（Heinz L. 等，2020年；张华等，2023年；陈晓等，2023年；Boeszoermeny A. 等，2023年）。TASL的激活可能涉及S294位点的磷酸化，这一点可由S294D突变体的磷酸模拟效应得到证实（Heinz L. 等，2020年）。尽管参与磷酸化TASL的激酶尚未完全阐明，但在人胚胎肾293（HEK293）细胞中TASL与TBK1、IKKε（IKBKE）或IKBKB激酶的共表达，以及在人白血病单核细胞THP1细胞中的敲除研究均暗示IKBKB（IKKβ）的参与（Heinz L. 等，2020年）。与SLC15A4结合的TASL招募转录因子IRF5，导致IRF5磷酸化和激活。此Reactome事件显示了TASL在S294位点的磷酸化。