Article
Structure of SHOC2-KRAS-PP1C complex reveals RAS isoform-specific determinants and insights into targeting complex assembly by RAS inhibitors.
Nature communications - 10 Jan 2026
Bonsor Daniel A, Finci Lorenzo I, Potter Jacob R, Young Lucy C, Wall Vanessa E, Goldstein de Salazar Ruby, Geis Katie R, Stephens Tyler, Finney Joseph, Nissley Dwight V, McCormick Frank, Simanshu Dhirendra K
Abstract excerpt
RAF activation is essential for MAPK signaling and is mediated by RAS binding and the dephosphorylation of a conserved phosphoserine by the SHOC2-RAS-PP1C complex. MRAS forms a high-affinity SHOC2-MRAS-PP1C (SMP) complex, while canonical RAS isoforms (KRAS, HRAS, NRAS) form analogous but lower-affinity assemblies. Yet, cancers driven by oncogenic KRAS, HRAS, or NRAS remain strongly SHOC2-dependent, suggesting...
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