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

Authors

Georg Vucak, Sebastian Didusch, Leandro Cannizzaro, Ana Santiago, Markus Hartl, Jörg Menche, Manuela Baccarini

Published in

Cell reports. Volume 45. Issue 11. Pages 118201. Oct 26, 2026. Epub Oct 26, 2026.

Abstract

The RAS/RAF/MEK/ERK pathway has been extensively studied for its roles in physiology and disease, yet a systems-level view of its interplay with the broader cellular context is lacking, limiting insight into paralog-specific roles, mutation-driven rewiring, and cross-pathway integration. To address this, we simultaneously mapped the interactomes of all pathway components and their activating and inactivating mutations, identifying 2,500 high-confidence interactors, 88% of which previously unreported, and generating a high-confidence, comprehensive reference map of the pathway in resting and activated states. The pathway behaves like a "molecular organism" that connects to other signaling complexes, operates from distinct subcellular sites, and integrates into networks relevant to physiology and disease. Dataset exploration uncovers paralog- and mutation-specific interaction signatures and pathway-level crosstalk, including previously unknown connections to mRNA metabolism and WNT signaling. The interactomes available at RAStoERK.univie.ac.at provide a foundational community resource for unbiased discovery, targeted mechanistic studies, and potential therapeutic exploration.

PMID:
42932306
Bibliographic data and abstract were imported from PubMed on 27 Oct 2026.

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