Fig 4.

Ras/MAPK signaling. Upon growth factor stimulation, the adaptor protein, Grb2, binds to specific phospho-tyrosine residues on activated receptors via its SH2 domain. Grb2 also binds to SOS and activates it at the plasma membrane, which then catalyzes the removal of GDP. Ras then rapidly binds GTP and adopts an active conformation. Activated Ras recruits Raf to the membrane leading to Raf kinase activation and resulting in phosphorylation and activation of MEK. Activated MEK, in turn phosphorylates ERK, so that it can subsequently activate its nuclear and non-nuclear substrates.