Reactome | IRAK1 phosphorylates Pellino upon TLR7/8 or 9 activation

IRAK1 phosphorylates Pellino upon TLR7/8 or 9 activation

Stable Identifier

R-HSA-975139

Type

Reaction [transition]

Species

Homo sapiens

Compartment

endosome membrane, cytosol

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)
      - MyD88 dependent cascade initiated on endosome (Homo sapiens)
        
        TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation (Homo sapiens)
        
        IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation (Homo sapiens)
        
        IRAK1 phosphorylates Pellino upon TLR7/8 or 9 activation (Homo sapiens)
    - Toll Like Receptor 9 (TLR9) Cascade (Homo sapiens)
      - MyD88 dependent cascade initiated on endosome (Homo sapiens)
        
        TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation (Homo sapiens)
        
        IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation (Homo sapiens)
        
        IRAK1 phosphorylates Pellino upon TLR7/8 or 9 activation (Homo sapiens)

General

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IRAK1 phosphorylates Pellino upon TLR7/8 or 9 activation

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Both IRAK1 and IRAK4 were shown to phosphorylate Pellino isoforms in vitro. The phosphorylation of Pellino proteins is a necessary step in enhancing of their E3 ubiquitin ligase activity. It remains unclear whether IRAK1(as shown here), IRAK4, or both protein kinases mediate the activation of Pellino isoforms in vivo.

Literature References

PubMed ID	Title	Journal	Year
19264966	Identification of the phosphorylation sites on the E3 ubiquitin ligase Pellino that are critical for activation by IRAK1 and IRAK4 Smith, H, Peggie, M, Campbell, DG, Vandermoere, F, Carrick, E, Cohen, P	Proc Natl Acad Sci U S A	2009
17675297	Kinase-active interleukin-1 receptor-associated kinases promote polyubiquitination and degradation of the Pellino family: direct evidence for PELLINO proteins being ubiquitin-protein isopeptide ligases Butler, MP, Hanly, JA, Moynagh, PN	J Biol Chem	2007
17997719	The IRAK-catalysed activation of the E3 ligase function of Pellino isoforms induces the Lys63-linked polyubiquitination of IRAK1 Ordureau, A, Smith, H, Windheim, M, Peggie, M, Carrick, E, Morrice, N, Cohen, P	Biochem J	2008