An activating Ras lesion is a parsimonious candidate, because Ras lies upstream of the branch to Raf and the branch to phosphoinositide 3-kinase. Persistent GTP-bound Ras can therefore produce both basal patterns through a single change. A lesion restricted to MEK would not directly explain the simultaneous Akt signal. The blot does not uniquely locate the mutation: a constitutively active upstream receptor tyrosine kinase or altered regulation of Ras could also activate both branches. Test the Ras nucleotide state, sequence relevant genes, and determine which targeted perturbation suppresses both outputs.

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