Activation of the platelet-derived growth factor receptor by the bovine papillomavirus E5 transforming protein.

Petti, Lisa M.; Nilson, Laura A.; DiMaio, Daniel

doi:10.1002/j.1460-2075.1991.tb08017.x

Cited by 214 publications

(204 citation statements)

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“…The role of the PDGF b receptor in transformation by the BPV E5 protein Expression of the BPV E5 protein induces constitutive activation of the PDGF b receptor in transformed cells (Petti et al, 1991), but it does not directly activate other receptors, including the closely related PDGF a receptor or the EGF receptor Petti and DiMaio, 1994). The PDGF b receptor activated by the BPV E5 protein shares several properties with the receptor activated by PDGF: it contains elevated levels of phosphotyrosine, displays increased in vitro tyrosine kinase activity, and is constitutively associated with various SH2 domaincontaining cellular proteins that play essential roles in the response to PDGF (Figure 1) (Cohen et al, 1993a;Drummond-Barbosa et al, 1995;Goldstein et al, 1994;Lai et al, 1998;Nilson and DiMaio, 1993;Petti and DiMaio, 1994;Petti et al, 1991).…”

Section: Bovine Papillomavirus E5 Proteinmentioning

confidence: 99%

“…The PDGF b receptor activated by the BPV E5 protein shares several properties with the receptor activated by PDGF: it contains elevated levels of phosphotyrosine, displays increased in vitro tyrosine kinase activity, and is constitutively associated with various SH2 domaincontaining cellular proteins that play essential roles in the response to PDGF (Figure 1) (Cohen et al, 1993a;Drummond-Barbosa et al, 1995;Goldstein et al, 1994;Lai et al, 1998;Nilson and DiMaio, 1993;Petti and DiMaio, 1994;Petti et al, 1991). Furthermore, like PDGF, the BPV E5 protein induces dimerization and trans-phosphorylation of the receptor .…”

Section: Bovine Papillomavirus E5 Proteinmentioning

confidence: 99%

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Mechanisms of cell transformation by papillomavirus E5 proteins

2001

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The papillomavirus E5 proteins are short, hydrophobic transforming proteins. The transmembrane E5 protein encoded by bovine papillomavirus transforms cells by activating the platelet-derived growth factor b receptor tyrosine kinase in a ligand-independent fashion. The bovine papillomavirus E5 protein forms a stable complex with the receptor, thereby inducing receptor dimerization and activation, trans-phosphorylation, and recruitment of cellular signaling proteins to the receptor. The E5 proteins of the human papillomaviruses also appear to a ect the activity of growth factor receptors and their signaling pathways. The interaction of papillomavirus E5 proteins with a subunit of the vacuolar ATPase may also contribute to transformation. Further analysis of these unique mechanisms of viral transformation will yield new insight into the regulation of growth factor receptor activity and cellular signal transduction pathways. Oncogene (2001) 20, 7866 ± 7873.

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Section: Bovine Papillomavirus E5 Proteinmentioning

confidence: 99%

Section: Bovine Papillomavirus E5 Proteinmentioning

confidence: 99%

Mechanisms of cell transformation by papillomavirus E5 proteins

2001

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“…The oncogenic activity of BPV-1 E5 is mediated principally by growth factor receptors, in particular the PDGF [3 receptor (Petti et al, 1991;Petti & DiMaio, 1994), although BPV-1 E5 can also co-operate with the EGF receptor, depending upon the cell type (Martin et al, 1989;Cohen et al, 1993).…”

Section: The Human Papillomavirus (Hpv)-6 and Hpv-16 E5 Proteins Co-omentioning

confidence: 99%

The human papillomavirus (HPV)-6 and HPV-16 E5 proteins co-operate with HPV-16 E7 in the transformation of primary rodent cells

Valle

Banks

1995

Journal of General Virology

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E5 is the smallest transforming protein encoded by the human papillomaviruses (HPVs). It has been shown to promote anchorage-independent growth in established NIH 3T3 cells, an activity that is enhanced in the presence of epidermal growth factor (EGF). It is thought that this activity of E5 is brought about by an increase in the half-life of stimulated EGF receptors, possibly through the perturbation of receptor processing. Recent studies have also shown that E5 can co-operate with HPV-16 E7 to stimulate proliferation of primary rodent cells. Using haemagglutinin I epitope-tagged E5 proteins, we have compared the mitogenic activity of HPV-6 and HPV-16 E5. Both tagged proteins retain the ability to bind to the cellular 16 kDa H+-ATPase protein.In addition, both HPV-6 and HPV-16 E5 retain the ability to co-operate with E7 in primary rodent cells, although E5 is considerably more active than HPV-6 E5 in these mitogenic assays. Interestingly, transfection of a plasmid over-expressing c-Raf appears to be capable of functionally substituting for E5 in the co-mitogen assays. Polyclonal cell lines derived from baby rat kidney cells co-transfected with E7 and E5 genes continue to express both the E5 and E7 mRNA, although the level of E5 expression is very low and protein cannot be detected. These polyclonal fines appear to be immortal and in some cases demonstrate anchorage-independent growth, an activity which is enhanced by the addition of EGF.

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“…This fusion protein, however, was not capable of transforming NIH 3T3 fibroblasts, suggesting that it functions differently from a hyperactive wild-type receptor. PDGFR-b has also been suggested to be a target for the E5-transforming protein of the bovine papilloma virus, as E5 has been shown to bind to and cause ligand-independent activation of the b-receptor (Petti et al, 1991(Petti et al, , 1997DiMaio, 1992, 1994). In vitro, wild-type PDGFR-b expression in NIH 3T3 fibroblasts is transforming (Uren et al, 1996;DeMali et al, 1997) as is wild-type PDGFR-a, although with lower potency (Yu et al, 1994a).…”

Section: Introductionmentioning

confidence: 99%

A human brain tumor-derived PDGFR-α deletion mutant is transforming

Clarke

Dirks

2003

Oncogene

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Aberrant receptor tyrosine kinase signaling plays an important role in the molecular pathogenesis of brain tumors. We have been studying a previously identified human glioblastoma-derived PDGFR-a mutant that has an in-frame deletion in the extracellular domain, causing loss of exons 8 and 9 (PDGFR-a D8,9 ). In the primary tumor, this deletion mutant receptor was shown to be amplified and overexpressed. The purpose of this study was to determine the expression, activity, localization, and transformation properties of this deletion mutant. In the absence of serum, or PDGF-AA, PDGFR-a D8,9 was phosphorylated on tyrosine residues, indicating ligandindependent autoactivation. Localization by staining and cell surface biotinylation studies revealed expression of the deletion mutant predominantly in the cytoplasm, with very little present on the cell surface. To determine if PDGFRa D8,9 was oncogenic, we transfected wild-type and mutant receptors into Rat1 cells and performed analyses of cell growth, in vitro transformation, and subcutaneous growth in the nude mouse. PDGFR-a D8,9 -expressing cells displayed enhanced cell growth and survival in low serum, and formed foci in monolayer cultures. PDGFR-a D8,9 -expressing Rat1 cells were also tumorigenic when injected subcutaneously into nude mice. Expression of PDGFRa D8,9 was also associated with increased c-Jun phosphorylation in the absence of PDGF ligand, demonstrating also that the mutant receptor is associated with altered intracellular signaling. These data demonstrate that PDGFR-a D8,9 is transforming, and it is the first demonstration of a naturally occurring tumor-derived mutant PDGFR-a with oncogenic properties.

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Activation of the platelet-derived growth factor receptor by the bovine papillomavirus E5 transforming protein.

Cited by 214 publications

References 47 publications

Mechanisms of cell transformation by papillomavirus E5 proteins

Mechanisms of cell transformation by papillomavirus E5 proteins

The human papillomavirus (HPV)-6 and HPV-16 E5 proteins co-operate with HPV-16 E7 in the transformation of primary rodent cells

A human brain tumor-derived PDGFR-α deletion mutant is transforming

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