FIGURE 16-21 Activation of Ras following ligand binding to receptor tyrosine kinases (RTKs) or cytokine receptors. The receptors for fibroblast growth factor (FGF) and many other growth factors are RTKs. The SH2 domain of the cytosolic adapter protein GRB2 binds to a specific phosphotyrosine on an activated, ligand-bound receptor, and the SH3 domains bind to the cytosolic Sos protein, bringing it near the cytosolic surface of the plasma membrane and close to its substrate, the inactive Ras·GDP. The guanine nucleotide exchange factor (GEF) activity of Sos then promotes formation of active Ras·GTP. Note that Ras is tethered to the cytosolic surface of the plasma membrane by a hydrophobic farnesyl anchor (see Figure 7-19). See J. Schlessinger, 2000, Cell 103:211, and M. A. Simon, 2000, Cell 103:13.