Characteristic KRAS signaling pathways. In the active guanosine triphosphate (GTP)-bound state, KRAS interacts with several families of effector proteins and stimulates their catalytic activities. Raf protein kinases activate mitogen-activated protein kinase kinases 1 and 2 (MEK1 and MEK2), which leads to extracellular-signal-regulated kinase (ERK)1/2 activation. Phosphoinositide 3-kinases (PI3Ks) generate second-messenger lipids and activate numerous target proteins, including the survival signaling kinase AkT. KRAS binding activates Ral-specific guanine nucleotide exchange factors (RalGEFs) by directing them to their Ral GTPase substrates in the plasma membrane. KRAS is indicated by a green frame shape, Raf/MEPK/ERK by an orange, PI3K/Ark/PDK1/mTOR by a sky blue, Ral by a brown, and GDP/GTP by a yellow circle. The nucleotide exchange factors (GEF) is indicated by a magenta, RALGEF and GTPase activating proteins (RALGAP)/RalGEF by a red, and ZONAB Sec5/Exo84/Filamin/RalBP1/PLD1 by a dark sea green rectangle.