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The inhibitors used target these mutant forms of KRAS, the downstream effectors MEK and ERK, and the upstream regulators SHP2 and SOS1. Comparisons of phosphoproteomes between cell lines revealed a core KRAS signaling signature and cell line\u2013specific signaling networks. In all cell lines, phosphoproteomes were dominated by different degrees of autonomous, oncogenic KRAS activity. Comparison of phosphoproteomes after short and long drug exposures revealed the temporal dynamics of KRAS-MEK-ERK axis inhibition that resulted in cell cycle exit. This transition to a quiescent state occurred in the absence of substantial proteome remodeling but included broad changes in protein phosphorylation and ubiquitylation. The collective data reveal insights into oncogenic KRAS signaling, place many additional proteins into this functional context, and implicate cell cycle exit as a mechanism by which cells evade death upon KRAS signaling inhibition.<\/jats:p>","DOI":"10.1126\/scisignal.adt6552","type":"journal-article","created":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T17:58:21Z","timestamp":1753811901000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":10,"title":["Proteomic analyses identify targets, pathways, and cellular consequences of oncogenic KRAS signaling"],"prefix":"10.1126","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1901-2488","authenticated-orcid":true,"given":"Nicole","family":"Kabella","sequence":"first","affiliation":[{"name":"School of Life Sciences, Technical University of Munich, Freising, 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