FIGURE 6.

Compartmentalized signaling of the NK₁R from endosomal membranes. 1: β-Arrestins (β-arrs) recruit the NK₁R, Src, MEKK, and ERK1/2 to endosomes and thereby assemble a signalosome that mediates ERK1/2 phosphorylation and activation. β-Arrestin-activated ERK1/2 translocate to the nucleus. 2: Under normal circumstances, ERK1/2 mediate the proliferative and anti-apoptotic actions of SP. 3: When ERK1/2 activation is abnormally sustained, as occurs in cells that lack active ECE-1, ERK1/2 phosphorylate and induce Nur77, which induces cell death.