Despite our anticipation that erbB4 would drive Ras activation, we found that erbB4 instead promotes MPNST pathogenesis via Ras-independent effects; these signaling events include alterations in the PI3K/Akt/mTOR and PLC-γ signaling cascades, activation of transcription via STAT proteins, and the phosphorylation of other molecules with oncogenic potential, such as HSP60. The gene discussed is AKT1; the disease is malignant peripheral nerve sheath tumor.