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 papillomavirus type 1 (BPV-1) is associated with its binding to, and activation of, both the platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) receptors. The E5 proteins of human papillomavirus types 6 and 16 (HPV-6, HPV-16) also transform rodent cells in the presence of the EGF receptor. In this study we examined whether epitope-tagged HPV E5 proteins could associate with three different tyrosine kinase-containing growth factor receptors: the EGF receptor, the erbB2 receptor, and the PDGF receptor. The HPV-6 E5 protein was found to associate 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 involve a similar mechanism unrelated to receptor binding (e.g., binding to the 16-kDa membrane pore protein) or that they proceed along distinct pathways, with receptor binding being important for HPV-6. Regardless of the ultimate mechanisms, the differences between the HPV-6 and HPV-16 E5 proteins in binding to growth factor receptors may potentially contribute to the distinctive morphologies of their respective neoplastic lesions.
Conrad
M
M
Georgetown University School of Medicine, Department of Pathology, Washington, DC 20007.
Goldstein
D
D
Andresson
T
T
Schlegel
R
R
D066246:ErbB Receptors / Q000378:metabolism; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases; D017978:Receptors, Growth Factor / Q000378:metabolism*; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D000086082:Viroporin Proteins
D066246:ErbB Receptors; D009856:Oncogene Proteins, Viral; D018719:Erb-b2 Receptor Tyrosine Kinases; D017978:Receptors, Growth Factor; D017479:Receptors, Platelet-Derived Growth Factor; D011993:Recombinant Fusion Proteins; C083104:E5 protein, Human papillomavirus type 6; C054859:oncogene protein E5, Human papillomavirus type 16; D000086082:Viroporin Proteins