The conserved C-terminal domain of the bovine papillomavirus E5 oncoprotein can associate with an alpha-adaptin-like molecule: a possible link between growth factor receptors and viral transformation.
The bovine papillomavirus E5 gene encodes an oncoprotein that can independently transform rodent fibroblasts. This small 44-amino-acid protein is thought to function through the activation of growth factor receptors. E5 activation of the epidermal growth factor receptor results in an increase in the number of activated receptors at the cell surface. This finding suggests that E5 may act by inhibiting the normal down regulation of activated epidermal growth factor receptor via coated pit-mediated endocytosis. We have constructed a fusion protein consisting of glutathione S-transferase and the conserved C-terminal domain of E5 (GST-E5) in order to identify E5-associated cellular proteins that may be involved in its transforming activity. We have identified a 125-kDa cellular protein with a strong associated serine kinase activity that specifically associated with GST-E5 in the reduced form but not with GST-E5 fusions that contained changes in several conserved amino acids. Microsequence and biochemical analyses suggest that p125 is a novel member of the alpha-adaptin family. Since alpha-adaptins have previously been shown to be involved in coated pit-mediated cell surface receptor endocytosis and down regulation, these results suggest that p125 may be an alpha-adaptin-like molecule involved in growth factor receptor down regulation and that E5 may act by inhibiting its activity.
Cohen
B D
BD
Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, Maryland 20892.
Lowy
D R
DR
Schiller
J T
JT
D016475:3T3 Cells; D033965:Adaptor Protein Complex alpha Subunits; D033942:Adaptor Proteins, Vesicular Transport; D000595:Amino Acid Sequence; D000818:Animals; D002472:Cell Transformation, Viral; D015536:Down-Regulation; D006133:Growth Substances / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000737:chemistry / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D017978:Receptors, Growth Factor / Q000378:metabolism*; D011993:Recombinant Fusion Proteins
D033965:Adaptor Protein Complex alpha Subunits; D033942:Adaptor Proteins, Vesicular Transport; D006133:Growth Substances; D009856:Oncogene Proteins, Viral; D011506:Proteins; D017978:Receptors, Growth Factor; D011993:Recombinant Fusion Proteins; C054304:oncogene protein E5, Bovine papillomavirus type 1; D011494:Protein Kinases