Fig. 1. Signal transduction and the Rab5 cycle. EGF stimulation leads to opposing effects on Rab5 nucleotide status. One pathway leads to an increase in active GTP-bound Rab5 and receptor internalisation through stimulation of nucleotide exchange, possibly through PI 3-kinase activation. Conversly, EGF stimulation can also negatively regulate endocytosis by activating the GTPase activity of Rab5 through the sequential recruitment of Eps8 and RN-tre to the receptor. Stimulation of endocytosis is also observed in response to p38 MAP-kinase activation by UV or peroxide (H2O2). This effect is proposed to be mediated through phosphorylation and activation of GDI, a chaperone of cytosolic GDP-bound Rab proteins, which results in a net increase in Rab5 cycling.
