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PMID: 7543592 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Mutational analysis of the interaction between the bovine papillomavirus E5 transforming protein and the endogenous beta receptor for platelet-derived growth factor in mouse C127 cells.

Journal of virology ·Vol. 69 ·No. 9 ·1995-09-00 ·Pages 5869-74

Nilson LA, Gottlieb RL, Polack GW, DiMaio D

Abstract

The bovine papillomavirus E5 protein is a 44-amino-acid membrane-associated protein that forms a stable complex with the endogenous platelet-derived growth factor (PDGF) beta receptor in rodent and bovine fibroblasts, resulting in sustained receptor activation and cell transformation. We report here that high-level expression of the E5 protein caused a reduction in the level of the mature form of the PDGF beta receptor in acutely and stably transformed mouse C127 cells. To explore in more detail the interaction of the E5 protein and the PDGF beta receptor, we tested the abilities of various E5 point mutants to bind the PDGF receptor, to induce PDGF receptor down-regulation and tyrosine phosphorylation, and to transform cells. A transformation-competent mutant, like the wild-type E5 protein, bound the receptor and induced receptor tyrosine phosphorylation and down-regulation. Transformation-defective E5 proteins either failed to interact with the endogenous PDGF beta receptor in mouse fibroblasts or underwent an aberrant interaction with the receptor. Mutation of glutamine at position 17, aspartic acid at position 33, or both carboxyl-terminal cysteine residues required for E5 homodimerization interfered with stable complex formation with the PDGF receptor, tyrosine phosphorylation and down-regulation of the receptor, and cell transformation. Point mutations at several other carboxyl-terminal positions generated transformation-defective E5 proteins that formed a complex with the PDGF receptor and induced receptor tyrosine phosphorylation but did not induce PDGF receptor down-regulation. Either PDGF receptor activation is not sufficient for transformation of C127 cells or the receptors that are tyrosine phosphorylated in response to these mutant E5 proteins are not fully activated and therefore are not able to deliver a mitogenic signal.

MeSH Terms
Amino Acid Sequence Animals Binding Sites Bovine papillomavirus 1/physiology Cell Line DNA Mutational Analysis Down-Regulation Frameshift Mutation Kinetics Mice Molecular Sequence Data Mutagenesis Mutagenesis, Site-Directed Oncogene Proteins, Viral/biosynthesis,isolation & purification,metabolism Phosphotyrosine Point Mutation Protein-Tyrosine Kinases/metabolism Receptor, Platelet-Derived Growth Factor beta Receptors, Platelet-Derived Growth Factor/isolation & purification,metabolism Recombinant Proteins/biosynthesis,isolation & purification,metabolism Tyrosine/analogs & derivatives,analysis
Chemicals
Oncogene Proteins, Viral Recombinant Proteins oncogene protein E5, Bovine papillomavirus type 1 Phosphotyrosine Tyrosine Protein-Tyrosine Kinases Receptor, Platelet-Derived Growth Factor beta Receptors, Platelet-Derived Growth Factor
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Nilson L A
Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Gottlieb R L
Polack G W
DiMaio D
References (36)
36 references, click to expand
  1. The bovine papillomavirus type 1 E5 transforming protein specifically binds and activates the beta-type receptor for the platelet-derived growth factor but not other related tyrosine kinase-containing receptors to induce cellular transformation.
    J Virol. 1994 Jul;68(7):4432-41 PMID: 8207816
  2. Platelet-derived growth factor. II. Specific binding to cultured cells.
    J Biol Chem. 1982 May 10;257(9):5161-71 PMID: 6279659
  3. An intact PDGF signaling pathway is required for efficient growth transformation of mouse C127 cells by the bovine papillomavirus E5 protein.
    Oncogene. 1995 Apr 6;10(7):1431-9 PMID: 7731695
  4. Ligand-independent activation of the platelet-derived growth factor beta receptor: requirements for bovine papillomavirus E5-induced mitogenic signaling.
    Mol Cell Biol. 1995 May;15(5):2570-81 PMID: 7739538
  5. Structural and functional studies on platelet-derived growth factor.
    EMBO J. 1992 Dec;11(12):4251-9 PMID: 1425569
  6. Surface binding and internalization of platelet-derived growth factor in human fibroblasts.
    Proc Natl Acad Sci U S A. 1983 Sep;80(18):5592-6 PMID: 6351063
  7. Platelet-derived growth factor: morphologic and biochemical studies of binding, internalization, and degradation.
    J Cell Physiol. 1984 Nov;121(2):263-74 PMID: 6092390
  8. Translation of open reading frame E5 of bovine papillomavirus is required for its transforming activity.
    Proc Natl Acad Sci U S A. 1986 Mar;83(6):1797-801 PMID: 3006073
  9. The E5 transforming gene of bovine papillomavirus encodes a small, hydrophobic polypeptide.
    Science. 1986 Jul 25;233(4762):464-7 PMID: 3014660
  10. Genetic and biochemical definition of the bovine papillomavirus E5 transforming protein.
    EMBO J. 1987 Aug;6(8):2381-5 PMID: 2822390
  11. 44-amino-acid E5 transforming protein of bovine papillomavirus requires a hydrophobic core and specific carboxyl-terminal amino acids.
    Mol Cell Biol. 1988 Oct;8(10):4071-8 PMID: 2847028
  12. Efficient transactivation and morphologic transformation by bovine papillomavirus genes expressed from a bovine papillomavirus/simian virus 40 recombinant virus.
    Proc Natl Acad Sci U S A. 1988 Dec;85(23):9007-11 PMID: 2848252
  13. The E5 oncoprotein of bovine papillomavirus is oriented asymmetrically in Golgi and plasma membranes.
    Virology. 1989 May;170(1):334-9 PMID: 2541554
  14. The bovine papillomavirus E5 transforming protein can stimulate the transforming activity of EGF and CSF-1 receptors.
    Cell. 1989 Oct 6;59(1):21-32 PMID: 2551505
  15. Transforming activity of a 16-amino-acid segment of the bovine papillomavirus E5 protein linked to random sequences of hydrophobic amino acids.
    J Virol. 1989 Nov;63(11):4515-9 PMID: 2552136
  16. Genetic evidence that acute morphologic transformation, induction of cellular DNA synthesis, and focus formation are mediated by a single activity of the bovine papillomavirus E5 protein.
    Mol Cell Biol. 1989 Dec;9(12):5563-72 PMID: 2555701
  17. Bovine papillomavirus E2 repressor mutant displays a high-copy-number phenotype and enhanced transforming activity.
    J Virol. 1990 Feb;64(2):944-9 PMID: 2153255
  18. Association between the PDGF receptor and members of the src family of tyrosine kinases.
    Cell. 1990 Aug 10;62(3):481-92 PMID: 1696179
  19. Oncogenes and signal transduction.
    Cell. 1991 Jan 25;64(2):281-302 PMID: 1846320
  20. Activation of the platelet-derived growth factor receptor by the bovine papillomavirus E5 transforming protein.
    EMBO J. 1991 Apr;10(4):845-55 PMID: 1849073
  21. Bovine papillomavirus E5 oncoprotein binds to the 16K component of vacuolar H(+)-ATPases.
    Nature. 1991 Jul 25;352(6333):347-9 PMID: 1649407
  22. Tumorigenic transformation of murine keratinocytes by the E5 genes of bovine papillomavirus type 1 and human papillomavirus type 16.
    J Virol. 1991 Dec;65(12):7078-83 PMID: 1658398
  23. A glutamine residue in the membrane-associating domain of the bovine papillomavirus type 1 E5 oncoprotein mediates its binding to a transmembrane component of the vacuolar H(+)-ATPase.
    J Virol. 1992 Jan;66(1):405-13 PMID: 1370089
  24. The central hydrophobic domain of the bovine papillomavirus E5 transforming protein can be functionally replaced by many hydrophobic amino acid sequences containing a glutamine.
    J Virol. 1992 Jan;66(1):505-11 PMID: 1727496
  25. Distinct phosphotyrosines on a growth factor receptor bind to specific molecules that mediate different signaling pathways.
    Cell. 1992 May 1;69(3):413-23 PMID: 1374684
  26. Localization of bovine papillomavirus type 1 E5 protein to transformed basal keratinocytes and permissive differentiated cells in fibropapilloma tissue.
    Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5665-9 PMID: 1319069
  27. Stable association between the bovine papillomavirus E5 transforming protein and activated platelet-derived growth factor receptor in transformed mouse cells.
    Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6736-40 PMID: 1323117
  28. The BPV-1 E5 protein, the 16 kDa membrane pore-forming protein and the PDGF receptor exist in a complex that is dependent on hydrophobic transmembrane interactions.
    EMBO J. 1992 Dec;11(13):4851-9 PMID: 1334459
  29. Platelet-derived growth factor receptor can mediate tumorigenic transformation by the bovine papillomavirus E5 protein.
    Mol Cell Biol. 1993 Jul;13(7):4137-45 PMID: 8321218
  30. Transformation-specific interaction of the bovine papillomavirus E5 oncoprotein with the platelet-derived growth factor receptor transmembrane domain and the epidermal growth factor receptor cytoplasmic domain.
    J Virol. 1993 Sep;67(9):5303-11 PMID: 8394451
  31. 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.
    Mol Cell Biol. 1993 Oct;13(10):6462-8 PMID: 8413245
  32. Disruption of PDGF receptor trafficking by mutation of its PI-3 kinase binding sites.
    Science. 1994 Feb 4;263(5147):684-7 PMID: 8303278
  33. Specific interaction between the bovine papillomavirus E5 transforming protein and the beta receptor for platelet-derived growth factor in stably transformed and acutely transfected cells.
    J Virol. 1994 Jun;68(6):3582-92 PMID: 8189497
  34. Cellular transformation by a transmembrane peptide: structural requirements for the bovine papillomavirus E5 oncoprotein.
    Proc Natl Acad Sci U S A. 1994 May 24;91(11):4634-8 PMID: 8197111
  35. Interaction of platelet-derived growth factor with its fibroblast receptor. Demonstration of ligand degradation and receptor modulation.
    J Biol Chem. 1982 Apr 25;257(8):4216-21 PMID: 6279627
  36. Mutation of the bovine papillomavirus E5 oncoprotein at amino acid 17 generates both high- and low-transforming variants.
    J Virol. 1994 Sep;68(9):6120-3 PMID: 8057494
Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.69.9.5869-5874.1995
Published
1995-09-00
Pages
5869-74
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC189463
Subset
IM
Grants
NCI NIH HHS · CA37157 · United States
External Links
PubMed source DOI: 10.1128/JVI.69.9.5869-5874.1995 PMC Full Text View journal details
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