Figure 1. Proposed model for TGFβ-induced polyubiquitination of p85α and AKT, activation of PI3K and AKT.

TGFβ ligands induce oligomerization of TGFβ receptors. TRAF6, which constitutively interacts with TβRI [6], undergoes autoubiquitination and ubiquitinates thereafter TβRI [7]. Then TRAF6 causes Lys63-linked polyubiquitination of p85α, leading to the activation of PI3K, production of PIP₃, and phosphorylation of AKT. Smad7, which is shown to have an adaptor function, is required for the recruitment of p85 and AKT [2, 5].