Reactome | TASL is phosphorylated

TASL is phosphorylated

Stable Identifier

R-HSA-9860264

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, endolysosome membrane

ReviewStatus

5/5

Locations in the PathwayBrowser

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Immune System (Homo sapiens)

- Innate Immune System (Homo sapiens)
  - Toll-like Receptor Cascades (Homo sapiens)
    - Toll Like Receptor 7/8 (TLR7/8) Cascade (Homo sapiens)
      - SLC15A4:TASL-dependent IRF5 activation (Homo sapiens)
        
        TASL is phosphorylated (Homo sapiens)
    - Toll Like Receptor 9 (TLR9) Cascade (Homo sapiens)
      - SLC15A4:TASL-dependent IRF5 activation (Homo sapiens)
        
        TASL is phosphorylated (Homo sapiens)

General

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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.

This Reactome events shows phosphorylation of TASL at S294.

Literature References

PubMed ID	Title	Journal	Year
32433612	TASL is the SLC15A4-associated adaptor for IRF5 activation by TLR7-9 Mbow, ML, Bensimon, A, Bigenzahn, JW, Sedlyarov, V, Rebsamen, M, Kapoor, U, Superti-Furga, G, Essletzbichler, P, Li, J, Heinz, LX, Pizzagalli, MD, Girardi, E, César-Razquin, A, Lee, J, Goldmann, U, Müller, AC, Scorzoni, S, Papakostas, K, Stefanovic, A, Whitehurst, CE, Kartnig, F, King, FJ	Nature	2020