FIGURE 7.

Schematic diagram of iron-induced upstream signaling. Iron signaling begins with generation of superoxide anion which causes PTP inhibition and consequent Src and p21^ras activation while mediating polyUb of TRAF6 leading to TAK1 activation in caveosomes of hepatic macrophages. Our earlier work (9) demonstrates that p21^ras, TAK1, and PI3K physically interact in caveosomes and these effectors and p21^ras-mediated and pI3K-modulated ERK1/2 activation, all contribute to IKK activation caused by iron.