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PMID: 2424008 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Phosphatidylinositol metabolism and polyoma-mediated transformation.

Kaplan DR, Whitman M, Schaffhausen B, Raptis L, Garcea RL, Pallas D, Roberts TM, Cantley L

Abstract

The effect of polyoma middle-sized tumor antigen (MTAg) on phosphatidylinositol metabolism has been characterized in vivo and in vitro using polyoma-transformed and polyoma-infected cells. Cells infected with transformation-competent polyoma virus exhibit increased levels of inositol phospholipids and the second messenger inositol trisphosphate. MTAg or pp60c-src immunoprecipitates from MTAg-transformed cells contain an activity that phosphorylates phosphatidylinositol and phosphatidylinositol 4-phosphate. This activity is induced in parallel with MTAg when the MTAg synthesis is regulated by hormonal or heavy metal inducers. Immunoprecipitates from one class of polyoma mutants defective in transformation have a reduced level of associated phosphatidylinositol kinase activity in vitro yet are capable of tyrosine phosphorylation on exogenous protein substrates at rates comparable to wild-type virus. Thus, for these mutants, phosphatidylinositol kinase activity is more tightly correlated with transformation than is protein kinase activity. These results suggest that alterations in phosphatidylinositol metabolism by MTAg play a role in transformation by polyoma virus.

MeSH Terms
Animals Antigens, Viral, Tumor/genetics Cell Transformation, Viral Mice Mutation Phosphatidylinositols/metabolism Phosphorylation Polyomavirus/immunology,physiology Protein-Tyrosine Kinases/metabolism Proto-Oncogene Proteins/metabolism Proto-Oncogene Proteins pp60(c-src) Rats
Chemicals
Antigens, Viral, Tumor Phosphatidylinositols Proto-Oncogene Proteins Protein-Tyrosine Kinases Proto-Oncogene Proteins pp60(c-src)
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Kaplan D R
Whitman M
Schaffhausen B
Raptis L
Garcea R L
Pallas D
Roberts T M
Cantley L
References (35)
35 references, click to expand
  1. Evidence that the Rous sarcoma virus transforming gene product phosphorylates phosphatidylinositol and diacylglycerol.
    Proc Natl Acad Sci U S A. 1984 Apr;81(7):2117-21 PMID: 6326105
  2. The role of protein kinase C in cell surface signal transduction and tumour promotion.
    Nature. 1984 Apr 19-25;308(5961):693-8 PMID: 6232463
  3. Inositol trisphosphate and diacylglycerol as second messengers.
    Biochem J. 1984 Jun 1;220(2):345-60 PMID: 6146314
  4. Monoclonal antibodies to Rous sarcoma virus pp60src react with enzymatically active cellular pp60src of avian and mammalian origin.
    J Virol. 1984 Aug;51(2):272-82 PMID: 6205164
  5. Inositol trisphosphate formation and calcium mobilization in Swiss 3T3 cells in response to platelet-derived growth factor.
    Biochem J. 1984 Aug 15;222(1):195-201 PMID: 6089758
  6. Hydrolysis of polyphosphoinositides by purified sheep seminal vesicle phospholipase C enzymes.
    J Biol Chem. 1984 Oct 10;259(19):11718-24 PMID: 6090445
  7. Enhancement of cellular src gene product associated tyrosyl kinase activity following polyoma virus infection and transformation.
    Cell. 1984 Oct;38(3):767-77 PMID: 6091900
  8. Inositol trisphosphate, a novel second messenger in cellular signal transduction.
    Nature. 1984 Nov 22-28;312(5992):315-21 PMID: 6095092
  9. Middle tumor antigen of polyomavirus transformation-defective mutant NG59 is associated with pp60c-src.
    J Virol. 1985 Jan;53(1):114-9 PMID: 2981329
  10. Oncogenes, ions, and phospholipids.
    Am J Physiol. 1985 Jan;248(1 Pt 1):C3-11 PMID: 2578254
  11. Association of phosphatidylinositol kinase activity with polyoma middle-T competent for transformation.
    Nature. 1985 May 16-22;315(6016):239-42 PMID: 2987699
  12. Evidence from two transformed cell lines that the phosphorylations of peptide tyrosine and phosphatidylinositol are catalyzed by different proteins.
    Proc Natl Acad Sci U S A. 1985 Jun;82(12):3993-7 PMID: 2987958
  13. Large-scale production of polyoma middle T antigen by using genetically engineered tumors.
    Mol Cell Biol. 1985 Jul;5(7):1795-9 PMID: 2991752
  14. Receptors and phosphoinositide-generated second messengers.
    Annu Rev Biochem. 1985;54:205-35 PMID: 2992357
  15. Residual transforming activity of PY1178T, a mutant lacking the principal in vitro tyrosine phosphorylation site, is not affected by removal of the secondary tyrosine phosphorylation site at residue 322.
    Virology. 1985 Jun;143(2):671-5 PMID: 2998034
  16. ras-transformed cells: altered levels of phosphatidylinositol-4,5-bisphosphate and catabolites.
    Science. 1986 Jan 24;231(4736):407-10 PMID: 3001936
  17. Regulation of cellular phenotype and expression of polyomavirus middle T antigen in rat fibroblasts.
    Mol Cell Biol. 1985 Sep;5(9):2476-86 PMID: 2426583
  18. Phosphatidylinositol kinase activities in normal and Rous sarcoma virus-transformed cells.
    Mol Cell Biol. 1985 Nov;5(11):3194-8 PMID: 3018507
  19. Cleavage of structural proteins during the assembly of the head of bacteriophage T4.
    Nature. 1970 Aug 15;227(5259):680-5 PMID: 5432063
  20. A difference in the breakdown of phosphatidylinositol in normal and SV40 transformed mouse fibroblasts.
    Biochem Biophys Res Commun. 1973 Nov 16;55(2):305-11 PMID: 4358397
  21. Polyoma virus-specific 55K protein isolated from plasma membrane of productively infected cells is virus-coded and important for cell transformation.
    Virology. 1979 Oct 15;98(1):261-6 PMID: 225866
  22. Identification of DNA sequence changes leading to loss of transforming ability in polyoma virus.
    J Biol Chem. 1980 Jan 10;255(1):230-5 PMID: 6243123
  23. Temperature-sensitive transformation by Rous sarcoma virus and temperature-sensitive protein kinase activity.
    J Virol. 1980 Jan;33(1):220-9 PMID: 6245228
  24. Middle T antigen as primary inducer of full expression of the phenotype of transformation by polyoma virus.
    J Virol. 1980 Jul;35(1):219-32 PMID: 6251270
  25. Transformation of rat cells by an altered polyoma virus genome expressing only the middle-T protein.
    Nature. 1981 Aug 13;292(5824):595-600 PMID: 6265803
  26. Characterization of polyoma mutants with altered middle and large T-antigens.
    J Virol. 1981 Sep;39(3):673-83 PMID: 6270343
  27. The polyphosphoinositide phosphodiesterase of erythrocyte membranes.
    Biochem J. 1981 Jul 15;198(1):133-40 PMID: 6275838
  28. Mutation causing premature termination of the polyoma virus medium T antigen blocks cell transformation.
    J Virol. 1982 Mar;41(3):1014-24 PMID: 6284958
  29. Carboxy terminus of polyoma middle-sized tumor antigen is required for attachment to membranes, associated protein kinase activities, and cell transformation.
    Proc Natl Acad Sci U S A. 1982 Jun;79(11):3579-83 PMID: 6179082
  30. Transforming genes and gene products of polyoma and SV40.
    CRC Crit Rev Biochem. 1982;13(3):215-86 PMID: 6293767
  31. Polyoma virus middle T antigen: relationship to cell membranes and apparent lack of ATP-binding activity.
    Mol Cell Biol. 1982 Oct;2(10):1187-98 PMID: 6184609
  32. Polyoma virus transforming protein associates with the product of the c-src cellular gene.
    Nature. 1983 Jun 2-8;303(5916):435-9 PMID: 6304524
  33. Transformation by polyoma virus is drastically reduced by substitution of phenylalanine for tyrosine at residue 315 of middle-sized tumor antigen.
    Proc Natl Acad Sci U S A. 1984 Feb;81(3):679-83 PMID: 6322163
  34. The complex of polyoma virus middle-T antigen and pp60c-src.
    EMBO J. 1984 Mar;3(3):585-91 PMID: 6325177
  35. Transforming protein of avian sarcoma virus UR2 is associated with phosphatidylinositol kinase activity: possible role in tumorigenesis.
    Proc Natl Acad Sci U S A. 1984 May;81(9):2728-32 PMID: 6326140
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1986-06-00
Pages
3624-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC323575
Subset
IM
Grants
NCI NIH HHS · CA34722 · United States
NIGMS NIH HHS · GM36133 · United States
NCI NIH HHS · CA3002 · United States
NCI NIH HHS · R01 CA037667 · United States
NCI NIH HHS · R01 CA034722 · United States
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