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The Q61H mutation decouples KRAS from upstream regulation and renders cancer cells resistant to SHP2 inhibitors.
Gebregiworgis T, Kano Y, St-Germain J, Radulovich N, Udaskin ML, Mentes A, Huang R, Poon BPK, He W, Valencia-Sama I, Robinson CM, Huestis M, Miao J, Yeh JJ, Zhang ZY, Irwin MS, Lee JE, Tsao MS, Raught B, Marshall CB, Ohh M, Ikura M. Gebregiworgis T, et al. Among authors: poon bpk. Nat Commun. 2021 Nov 1;12(1):6274. doi: 10.1038/s41467-021-26526-y. Nat Commun. 2021. PMID: 34725361 Free PMC article.
Tyrosyl phosphorylation of KRAS stalls GTPase cycle via alteration of switch I and II conformation.
Kano Y, Gebregiworgis T, Marshall CB, Radulovich N, Poon BPK, St-Germain J, Cook JD, Valencia-Sama I, Grant BMM, Herrera SG, Miao J, Raught B, Irwin MS, Lee JE, Yeh JJ, Zhang ZY, Tsao MS, Ikura M, Ohh M. Kano Y, et al. Among authors: poon bpk. Nat Commun. 2019 Jan 15;10(1):224. doi: 10.1038/s41467-018-08115-8. Nat Commun. 2019. PMID: 30644389 Free PMC article.