Figure 1.

The MAPK cascade. Once a ligand binds the tyrosine kinase receptor, it self-phosphorylates [18]. This creates binding sites for Shc and Shp2. GRB2 can associate with either and then recruit SOS [19,20]. SOS is a guanine exchange factor for Ras and induces the exchange of GDP for GTP [21]. Now active Ras will dimerize and bind Raf [21]. After activating Raf, GTPase activating proteins (GAP) will hydrolyze the GTP to GDP to return Ras to its resting inactive state [22]. The active Raf dimers will recruit MEK [23], which then activates ERK [3]. ERK interacts with Importin 7 at the nuclear envelope to facilitate its entry through the nuclear pore complex into the nucleus [24,25]. Once inside, it phosphorylates multiple transcription factors to alter gene expression in the cell and induce proliferation and survival [26].