Article
Structural and functional analyses of a germline KRAS T50I mutation provide insights into Raf activation.
JCI insight - 8 Sept 2023
Chen Pan-Yu, Huang Benjamin J, Harris Max, Boone Christopher, Wang Weijie, Carias Heidi, Mesiona Brian, Mavrici Daniela, Kohler Amanda C, Bollag Gideon, Zhang Chao, Zhang Ying, Shannon Kevin
Abstract excerpt
A T50I substitution in the K-Ras interswitch domain causes Noonan syndrome and emerged as a third-site mutation that restored the in vivo transforming activity and constitutive MAPK pathway activation by an attenuated KrasG12D,E37G oncogene in a mouse leukemia model. Biochemical and crystallographic data suggested that K-RasT50I increases MAPK signal output through a non-GTPase mechanism, potentially by promoting...
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