Figure 4

Model of cellular events during cell transformation mediated by BPV-1 E5. E5 binds to the transmembrane domain of PDGFβ-R and induces receptor dimerisation and autophosphorylation. The activated receptor can recruit p85-PI3K that activates the AKT and JNK pathway. PDGFβR stimulation of a PI3K-AKTpathway leads to increased expression of cyclin D3. Recruitment of Sos1-GRB2 complex to p-PDGFβR may activate Ras, although the downstream MAPK pathway is not activated; therefore Ras may activate PI3-K pathway. The SHP2-p66Shc complex bound to the activated PDGFβ-R may be recruited and inactivates p190BRhoGAP, resulting in activation of a Rho family GTPase, Rho A and its downstream effector ROCK inducing focus formation. E5 is able to interact with c-src in late endosomal and trans-Golgi compartment, thus resulting in c-src constitutively activation. E5 interacts with the C-terminus of MHC I heavy chain and causes the retention of MHC I in the Golgi apparatus, thus preventing its transport to the cell surface. E5 perturbs the physiological activity of the V-ATPase by inhibiting the correct assembly of V-ATPase and H+ pumping, thus inducing persistent alkalinization of the Golgi and endosomes vescicles.