Fig. 2

RAS proteins play a pivotal role in the regulation of cell proliferation, differentiation, and survival through various signal transduction cascades, including the canonical RAF–MEK–ERK/MAPK, PI3K–AKT–mTOR, and RALGDS–RAL pathways. Once the ligand binds to the extracellular domain of the RTK, the signal is transmitted through the transmembrane domain resulting in RTK dimerization and subsequent RAS activation. RAS signaling is further regulated by a balance between activation by GEF’s (e.g., SOS and RASGRP) and inactivation by GAP’s (e.g., NF and p120GAP). Abbreviations: RTK, receptor tyrosine kinase; GEF’s, guanine nucleotide exchange factors; GAP’s, GTPase-activating proteins; SOS, son of sevenless homologue; RASGRP, RAS guanyl nucelotide-releasing protein; NF, neurofibromin