MyD88 and Tollip only bind to non-phosphorylated IRAK1 (Wesche et al. 1997) so hyper-phosphorylated IRAK1 is predisposed to release from the receptor complex, a key step in this signaling cascade. It is believed that the interaction of IRAK1 with TRAF6 enables the release of IRAK1:TRAF6 from the receptor (Gottipati et al. 2007). Though released from the receptor complex, IRAK1:TRAF6 remains associated with the membrane, perhaps due to subsequent interaction with the TAK1 complex (Dong et al. 2006).
Gottipati, S, Rao, NL, Fung-Leung, WP
IRAKM prevents the dissociation of IRAK1 and IRAK4 from MYD88 thereby inhibiting the formation of IRAK1-TRAF6 complexes.
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