Bovine papillomavirus E5 protein induces the formation of signal transduction complexes containing dimeric activated platelet-derived growth factor beta receptor and associated signaling proteins.
The bovine papillomavirus E5 protein binds to the cellular platelet-derived growth factor (PDGF) beta receptor, resulting in constitutive activation of the receptor and cell growth transformation. By subjecting extracts from E5-transformed or PDGF-treated cells to velocity sedimentation in sucrose gradients, activated PDGF beta receptor complexes were separated from monomeric, inactive receptor. Rapidly sedimenting activated complexes contained oligomeric (apparently dimeric), tyrosine-phosphorylated PDGF beta receptor, the E5 protein, and associated cellular signaling proteins including the p85 subunit of phosphoinositol 3'-kinase, phospholipase Cgamma, and Ras-GTPase activating protein. These signaling proteins made the major contribution to the increased sedimentation rate of the activated receptor complexes. Pairwise analysis of components of these complexes indicated that multiple signaling proteins and the E5 protein were simultaneously present in the activated complexes. Our results also showed that the E5 protein and PDGF activated only a small fraction of the total PDGF beta receptor, that not all receptor molecules associated with the E5 protein were tyrosine-phosphorylated, and that signaling proteins could bind to hemiphosphorylated receptor dimers. On the basis of these results, we propose a model for the assembly of multiprotein, activated PDGF beta receptor complexes in response to the E5 protein.
Lai
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Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Henningson
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DiMaio
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D052688:Bovine papillomavirus 1 / Q000502:physiology*; D002460:Cell Line; D002472:Cell Transformation, Viral; D019281:Dimerization; D009856:Oncogene Proteins, Viral / Q000502:physiology*; D011233:Precipitin Tests; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D009856:Oncogene Proteins, Viral; C054304:oncogene protein E5, Bovine papillomavirus type 1; D020797:Receptor, Platelet-Derived Growth Factor beta