Fig. 2.

Postulated regulatory mechanisms of Il-1 by BACE1 activity. Il1-R2 regulation of Il-1 signaling. (1) Il-1α or Il-1β binds Il1-R1 and Il-1RAcP, resulting in normal signaling. (2) Il1-R2 binds Il-1RAcp and either Il-1α or Il-1β but does not result in signaling. (3) Il1-R2 can regulate Il-1 signaling by binding Il-1RAcP and which leaves it unable to complex with interleukin 1 receptor (Il-1R1) for signaling. (4) Il1-R2 can be secreted or shed by cells and can bind Il-1α and Il-1β extracellularly and prevent them from binding Il-1R1/Il-1RAcP. (5) BACE1 is one of a few enzymes capable of cleaving Il1-R2. BACE1 activity could influence the relative amounts of Il-R2 present in the cell membrane or shed into extracellular space. (6) Intracellular Il1-R2 can bind either pro-Il-1α or pro-Il-1β and prevent cleavage by calpain or caspase-1, respectively, for activation