THE E5 PROTEIN OF HPV-6, BUT NOT HPV-16, ASSOCIATES EFFICIENTLY WITH CELLULAR GROWTH-FACTOR RECEPTORS

The transforming activity of the prototype E5 protein of bovine papill omavirus type 1 (BPV-1) is associated with its binding to, and activat ion of, both the platelet-derived growth factor (PDGF) and epidermal g rowth factor(EGF) receptors. The E5 proteins of human papillomavirus t ypes 6 and 16 (HPV-6, HPV-16) also transform rodent cells in the prese nce of the EGF receptor. In this study we examined whether epitope-tag ged HPV E5 proteins could associate with three different tyrosine kina se-containing growth factor receptors: the EGF receptor, the erbB2 rec eptor, and the PDGF receptor. The HPV-6 E5 protein was found to associ ate efficiently with all three of these growth factor receptors, while the HPV-16 E5 protein did not. These findings suggest either that the in vitro transforming activities of HPV-6 and HPV-16 E5 proteins invo lve a similar mechanism unrelated to receptor binding (e.g., binding t o the 16-kDa membrane pore protein) or that they proceed along distinc t pathways, with receptor binding being important for HPV-6. Regardles s of the ultimate mechanisms, the differences between the HPV-6 and HP V-16 E5 proteins in binding to growth factor receptors may potentially contribute to the distinctive morphologies of their respective neopla stic lesions. (C) 1994 Academic Press, Inc.