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Ras

RAS proteins are binary switches, cycling between ON and OFF states during signal transduction. In normal mammalian cells, RAF kinases (ARAF, BRAF, and CRAF) are major RAS effectors. Ras1 activates a MAP kinase cascade, although in this organism, the kinase that Ras1 activates directly, Byr2, does not resemble RAF. On the other hand, RAS proteins (RAS1p and RAS2p) activate adenylate cyclase and regulate production of cyclic AMP (cAMP) in response to intracellular glucose. Mutations in RAS regulators, such as neurofibromin and SPRED1, also make significant contributions to cancer. Abnormal RAS activity may also play a significant role in autism and other neurological disorders. RAS proteins are binary molecular switches that cycle between active guanosine triphosphate (GTP)-bound and inactive guanosine diphosphate (GDP)-bound states. This switch mechanism has been highly conserved among GDP/GTP binding proteins as diverse as bacterial elongation factors, heterotrimeric G-proteins, and a myriad of small GTPases with diverse biological functions.  
GEFs and GAPs are large, multi-domain proteins capable of an astonishing variety of interactions with other proteins, lipids, and regulatory molecules that control levels of active and inactive RAS. Dependence of RAS and other GTPases on GEFs and GAPs to switch them on and off allows both processes to be highly regulated and responsive to multiple signal inputs. RAS proteins activate effectors by recruitment to the plasma membrane. Indeed, for RAF kinase, translocation appears to be sufficient to initiate the complicated activation process. Recruitment of RalGDS to RAS in the plasma membrane leads to activation of RalA and RalB. Recruitment of PI 3-kinase γ (PI3Kγ) to the plasma membrane through a myristoylation signal rescues a mutant that does not bind RAS, suggesting membrane recruitment is a critical step in the activation process.   RAS proteins play a causal role in human cancer: this has been recognized for many years and has inspired multiple attempts to find RAS inhibitors.

References

1.Simanshu DK,et al. Cell. 2017;170(1):17–33.