RAStoERK: A reference interaction atlas for insights into signaling and disease.

RAStoERK simultaneously mapped interactomes of all RAS/RAF/MEK/ERK components and their activating/inactivating mutations, identifying 2,500 high-confidence interactors, 88% previously unreported.

• Why it matters: A systems-level view of how this pathway interfaces with broader cellular context is missing, limiting understanding of paralog-specific roles, mutation-driven rewiring, and cross-pathway integration.
• What they did: The team generated a high-confidence reference interaction map of the pathway in resting and activated states by mapping interactomes for pathway components and their activating/inactivating mutations.
• The result: Dataset exploration reveals paralog- and mutation-specific interaction signatures and pathway-level crosstalk, including previously unknown connections to mRNA metabolism and WNT signaling, enabling unbiased discovery and mechanistic/therapeutic exploration.