Reactome | hp-IRAK1,hp-IRAK4 bind Pellino1,2,3

hp-IRAK1,hp-IRAK4 bind Pellino1,2,3

Stable Identifier

R-HSA-450690

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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IRAK1 and 4 interact with Pellino-1 (Jiang et al. 2003), 2 (Strellow et al. 2003) and 3 (Butler et al. 2005, 2007). Pellinos may act as scaffolding proteins, bringing signaling complexes into proximity. They are E3 ubiquitin ligases capable of ubiquitinating IRAK1, believed to mediate IL-1-stimulated formation of K63-polyubiquitinated IRAK1 in cells.

Though not clearly demonstrated and therefore not shown here, the current models of IRAK1 involvement suggest it would be within a complex including TRAF6.

Literature References

PubMed ID	Title	Journal	Year
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 Hanly, JA, Butler, MP, Moynagh, PN	J Biol Chem	2007
12496252	Pellino 1 is required for interleukin-1 (IL-1)-mediated signaling through its interaction with the IL-1 receptor-associated kinase 4 (IRAK4)-IRAK-tumor necrosis factor receptor-associated factor 6 (TRAF6) complex Johnson, HJ, Li, X, Jiang, Z, Nie, H, Bird, TA, Qin, J	J Biol Chem	2003
15917247	Pellino3 is a novel upstream regulator of p38 MAPK and activates CREB in a p38-dependent manner Hanly, JA, Butler, MP, Moynagh, PN	J Biol Chem	2005
12860405	Characterization of Pellino2, a substrate of IRAK1 and IRAK4 Wesche, H, Strelow, A, Kollewe, C	FEBS Lett	2003
17997719	The IRAK-catalysed activation of the E3 ligase function of Pellino isoforms induces the Lys63-linked polyubiquitination of IRAK1 Peggie, M, Ordureau, A, Carrick, E, Morrice, N, Windheim, M, Smith, H, Cohen, P	Biochem J	2008