The bovine papillomavirus E5 transforming protein can stimulate the transforming activity of EGF and CSF-1 receptors.
The bovine papillomavirus E5 transforming gene encodes a 44 amino acid protein product that is localized to cytoplasmic membranes, including the plasma membrane. We now report that E5 can cooperate with human EGF receptors and with human CSF-1 receptors to induce cellular transformation of NIH 3T3 cells. Cooperation occurred in the absence of receptor stimulation by ligand, and it was further augmented by treatment with ligand. Cooperation was not seen between E5 and either c-fes or c-src. The cooperation between E5 and high levels of EGF receptors was associated with inhibition of receptor degradation and persistence of activated receptors on the cell surface. We conclude that E5 may enhance the receptor activity via inhibition of receptor down-modulation.
Martin
P
P
Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, Maryland 20892.
Vass
W C
WC
Schiller
J T
JT
Lowy
D R
DR
Velu
T J
TJ
D000818:Animals; D052688:Bovine papillomavirus 1 / Q000502:physiology*; D002460:Cell Line; D002472:Cell Transformation, Viral; D003115:Colony-Stimulating Factors / Q000378:metabolism*; D004357:Drug Synergism; D066246:ErbB Receptors / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D051379:Mice; D009856:Oncogene Proteins, Viral / Q000502:physiology*; D027383:Papillomaviridae / Q000502:physiology*; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000502:physiology; D011956:Receptors, Cell Surface / Q000378:metabolism / Q000502:physiology*; D016184:Receptors, Colony-Stimulating Factor; D015291:Transforming Growth Factors / Q000096:biosynthesis
D003115:Colony-Stimulating Factors; D009856:Oncogene Proteins, Viral; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D016184:Receptors, Colony-Stimulating Factor; C054304:oncogene protein E5, Bovine papillomavirus type 1; D015291:Transforming Growth Factors; D066246:ErbB Receptors