Figure 5

Schematic model of signaling events of OPN induced Erk1/2 activation in prostate cancer cells. OPN binds to PC3 cells by means of the CD44 receptor and integrins at the plasma membrane. Here we show that OPN phosphorylates c-Raf (Ser 338), a marker of c-Raf activation, leading to downstream activation of MEK1/2. OPN activates Akt as well. Akt activity has been shown to phosphorylate c-Raf (Serine 259) which is an inhibitory site of the Raf proteins therefore blocking increased activation of c-Raf. Thus, although OPN induces overall Erk1/2 activation, it also has an inhibitory effect on Erk1/2 through the activation of Akt.