"Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ"

"we characterized the most common KRAS mutants biochemically for substrate binding kinetics, intrinsic and"

"SIRT2-mediated lysine defatty-acylation promotes endomembrane localization of K-Ras4a"

"Active RAS recruits RAF to the membrane where RAF dimerizes and becomes active"

"The canonical RAS family members HRAS, KRAS, and NRAS (H/K/NRAS) also bind SHOC2"

"SOS1 facilitates the exchange of GDP to GTP thereby leading to activation of KRAS"

"Their interaction plays a crucial role in activating PI3Kα and amplifying the PI3K-AKT-mTOR pathway"

"GTP-bound RAS recruits RAF (the MAPK kinase kinase), and promotes its dimerization and activation"

"After farnesylation, C-terminal proteolysis, carboxymethylation and palmitoylation"

"RAS proteins have weak intrinsic GTPase activity in the absence of other effectors"

"Ras proteins bind GDP/GTP and possess intrinsic GTPase activity"

"Alternates between an inactive form bound to GDP and an active form bound to GTP"

"Cell membrane {ECO:0000269|PubMed:22431598, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:29239724}; Lipid-anchor"

"A widely cited expert synthesis reports Ras intrinsic hydrolysis is slow (kcat ≈ 2×10−4 s−1), but it is a real enzymatic activity central to the molecular switch."

"GAPs accelerate Ras hydrolysis (reported up to ~10^5-fold in expert synthesis) and do so by complementing the active site, including an external arginine ("arginine finger") concept; importantly, Gly12 oncogenic mutants are classically noted to resist such stimulation."

"Primary structural evidence for Ras activation by SOS comes from the crystal structure of Ras in complex with the SOS catalytic region, indicating SOS stabilizes Ras in a nucleotide-free state, a mechanistic basis for GEF-driven exchange."

"Structure-guided mutagenesis further shows distinct roles for Ras switch I vs switch II: switch II interactions largely anchor Ras to SOS, while switch I perturbation disrupts the nucleotide-binding site to promote GDP dissociation."

"A primary structural and functional demonstration of Ras effector engagement is the Ras–PI3Kγ complex: PI3Kγ is directly activated by GTP-loaded Ras, and the structure shows Ras uses switch I/II to bind the PI3Kγ Ras-binding domain."

"KRAS4A contains a palmitoylation site (Cys180) enabling reversible palmitoylation-dependent Golgi trafficking. Expert synthesis notes that farnesylation + palmitoylation can increase membrane affinity by >100-fold and acts as a Golgi "affinity trap" promoting vesicular delivery to the plasma membrane."

"KRAS4B lacks palmitoylatable cysteines and instead uses a lysine-rich polybasic HVR (reported net charge +8) to electrostatically stabilize plasma membrane association with anionic lipids."

"KRAS4B (and depalmitoylated prenylated cargo) can bind PDE6D to shield its prenyl group and support trafficking between endomembranes and plasma membrane. Quantitatively summarized evidence indicates that loss of KRAS4B carboxymethylation reduces PDE6D affinity by >35-fold, and a Ser181 phosphomimic (S181E) reduces affinity by >6-fold."

"Downstream phenotypes (proliferation, senescence, apoptosis, transcriptional programs, developmental and immune/metabolic outcomes) are highly context dependent and often derived from mutant/overexpression models. These should not be propagated as WT KRAS GO BP annotations without direct WT evidence."