VEGFR2 stimulates ERK not via GRB2-SOS-RAS, but via pY1175-dependent phosphorylation of PLC gamma and subsequent activation of PKCs. PKC plays an important mediatory role in the proliferative Ras/Raf/MEK/ERK pathway. PKC alpha can intersect the Ras/Raf/MEK/ERK cascade at the level of Ras (Clark et al. 2004) or downstream of Ras through direct phosphorylation of Raf (Kolch et al. 1993). VEGF stimulation leads to Ras activation in a Ras-guanine nucleotide exchange factor (GEF) independent mechanism. It rather relies on modulating the regulation of Ras-GTPase activating protein (GAP) than regulation of Ras-GEFS (Wu et al. 2003).