Transforming Growth Factor - Beta (TGFß) Stimulated Isoform Specific Activation of akt2 via Ras Mediates Epithelial-Mesenchymal Transition (EMT)

TGFß induces epithelial-mesenchymal transdifferentiation (EMT) accompanied by cellular differentiation and migration. EMT has emerged as a fundamental process governing embryonic development, adult tissue homeostasis and metastatic progression. Our lab had earlier identified a post-transcriptional pathway by which TGFß modulates expression of EMT-specific proteins. It was shown that heterogeneous nuclear ribonucleoprotein E1 (hnRNP E1) binds a structural, 33 nucleotides (nt) TGF beta-activated translation (BAT) element in the 3\u27-UTR of disabled-2 (Dab2) and interleukin-like EMT inducer (ILEI)transcripts, and repress their translation. This inhibition is removed following hnRNP E1 phosphorylation by activated Akt2. We now show that specific activation of Akt2, and not Akt1, following TGFß stimulation is Ras dependent and we provide evidence which suggest that Ras mediates a complex formation between activated TGFß receptors and ShcA, which in turn potentiates the complex in order to specifically recruit Akt2, and not Akt