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- W2892639632 endingPage "1282" @default.
- W2892639632 startingPage "1263" @default.
- W2892639632 abstract "Autoinhibition is an effective mechanism that guards proteins against spurious activation. Despite its ubiquity, the distinct organizations of the autoinhibited states and their release mechanisms differ. Signaling is most responsive to the cell environment only if a small shift in the equilibrium is required to switch the system from an inactive (occluded) to an active (exposed) state. Ras signaling follows this paradigm. This underscores the challenge in pharmacological intervention to exploit and enhance autoinhibited states. Here, we review autoinhibition and release mechanisms at the membrane focusing on three representative Ras effectors, Raf protein kinase, PI3Kα lipid kinase, and NORE1A (RASSF5) tumor suppressor, and point to the ramifications to drug discovery. We further touch on Ras upstream and downstream signaling, Ras activation, and the Ras superfamily in this light, altogether providing a broad outlook of the principles and complexities of autoinhibition." @default.
- W2892639632 created "2018-10-05" @default.
- W2892639632 creator A5001283984 @default.
- W2892639632 creator A5020262392 @default.
- W2892639632 creator A5025357844 @default.
- W2892639632 creator A5043941930 @default.
- W2892639632 creator A5058080897 @default.
- W2892639632 creator A5071084031 @default.
- W2892639632 date "2018-09-29" @default.
- W2892639632 modified "2023-10-16" @default.
- W2892639632 title "Autoinhibition in Ras effectors Raf, PI3Kα, and RASSF5: a comprehensive review underscoring the challenges in pharmacological intervention" @default.
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