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Targeting RAS phosphorylation in cancer therapy: Mechanisms and modulators

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Summary: The dual phosphorylation of K-Ras induces structural changes affecting nucleotide and catalytic sites, reducing the catalytic competence and signal delivery abilities of GAP, SOS, and Raf. Phosphorylation also disrupts the Ras/Raf interface allosteric pathway, altering the distribution of Ras-GTP sub-states and identifying potential druggable pockets. These findings highlight the impact of phosphorylation on Ras function and signal transduction, suggesting it as a target for cancer drug discovery.

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