Home LiteratureArticle Details
PMID: 2582236 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Low level of cellular protein phosphorylation by nontransforming overproduced p60c-src.

Molecular and cellular biology ·Vol. 5 ·No. 5 ·1985-05-00 ·Pages 1058-66

Iba H, Cross FR, Garber EA, Hanafusa H

Abstract

We have previously found that Rous sarcoma virus variants in which the viral src (v-src) gene is replaced by the cellular src (c-src) gene have no transforming activity. In this study, we analyzed the basis for the inability of the p60c-src overproduced by these variants to transform cells. Phosphorylations of tyrosine residues in total cell protein or in cellular 34K protein are known to be markedly enhanced upon infection with wild-type Rous sarcoma virus. We found that these tyrosine phosphorylations were only slightly increased in the c-src-containing virus-infected cells, whereas both levels were significantly increased by infection with wild-type Rous sarcoma virus, or transforming mutant viruses which are derived from c-src-containing viruses by spontaneous mutation. Phosphorylation at tyrosine 416 of p60 itself was also extremely low in overproduced p60c-src and high in p60s of transforming mutant viruses. In immunoprecipitates with monoclonal antibody, the overproduced p60c-src had much lower casein tyrosine kinase activity than did p60v-src. We previously showed that p60 myristylation and plasma membrane localization may be required for cell transformation. p60c-src was similar to transforming p60s in these properties. These results strongly suggest that the low level of tyrosine phosphorylation by overproduced p60c-src accounts for its inability to transform cells.

MeSH Terms
Animals Antigen-Antibody Complex Avian Sarcoma Viruses/genetics Cell Compartmentation Cell Membrane/metabolism Cell Transformation, Viral Chick Embryo Macromolecular Substances Molecular Weight Mutation Myristic Acid Myristic Acids/metabolism Peptide Fragments/analysis Phosphoproteins/metabolism Phosphorylation Protein Kinases/metabolism Protein Processing, Post-Translational Protein-Tyrosine Kinases Proto-Oncogene Proteins pp60(c-src) Tyrosine/metabolism
Chemicals
Antigen-Antibody Complex Macromolecular Substances Myristic Acids Peptide Fragments Phosphoproteins Myristic Acid Tyrosine Protein Kinases Protein-Tyrosine Kinases Proto-Oncogene Proteins pp60(c-src)
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Iba H
Cross F R
Garber E A
Hanafusa H
References (55)
55 references, click to expand
  1. A cellular protein that associates with the transforming protein of Rous sarcoma virus is also a heat-shock protein.
    Proc Natl Acad Sci U S A. 1981 Feb;78(2):1067-71 PMID: 6262754
  2. Four different classes of retroviruses induce phosphorylation of tyrosines present in similar cellular proteins.
    Mol Cell Biol. 1981 May;1(5):394-407 PMID: 6086011
  3. Two cellular proteins that immunoprecipitate with the transforming protein of Rous sarcoma virus.
    Virology. 1981 Sep;113(2):736-51 PMID: 6267806
  4. The specific interaction of the Rous sarcoma virus transforming protein, pp60src, with two cellular proteins.
    Cell. 1981 Aug;25(2):363-72 PMID: 6269742
  5. Characterization of sites for tyrosine phosphorylation in the transforming protein of Rous sarcoma virus (pp60v-src) and its normal cellular homologue (pp60c-src).
    Proc Natl Acad Sci U S A. 1981 Oct;78(10):6013-7 PMID: 6273838
  6. Analysis of the sequence of amino acids surrounding sites of tyrosine phosphorylation.
    Proc Natl Acad Sci U S A. 1982 Feb;79(4):973-7 PMID: 6280176
  7. Evidence the pp60src, the product of the Rous sarcoma virus src gene, undergoes autophosphorylation.
    J Virol. 1982 Jan;41(1):1-7 PMID: 6283105
  8. Cellular sequences related to three new onc genes of avian sarcoma virus (fps, yes, and ros) and their expression in normal and transformed cells.
    J Virol. 1982 Apr;42(1):143-52 PMID: 6177868
  9. Phosphorylation and metabolism of the transforming protein of Rous sarcoma virus.
    J Virol. 1982 Mar;41(3):813-20 PMID: 6178840
  10. Role of p60src kinase activity in the induction of neuroretinal cell proliferation by rous sarcoma virus.
    J Virol. 1982 Jun;42(3):780-9 PMID: 6284995
  11. Half-life of the Rous sarcoma virus transforming protein pp60src and its associated kinase activity.
    Mol Cell Biol. 1982 Apr;2(4):355-60 PMID: 6287235
  12. DNA sequence of the viral and cellular src gene of chickens. 1. Complete nucleotide sequence of an EcoRI fragment of recovered avian sarcoma virus which codes for gp37 and pp60src.
    J Virol. 1982 Oct;44(1):1-11 PMID: 6292477
  13. Development of anti-pp60src serum with antigen produced in Escherichia coli.
    J Virol. 1983 Jan;45(1):462-5 PMID: 6401819
  14. Transit of pp60v-src to the plasma membrane.
    Proc Natl Acad Sci U S A. 1982 Dec;79(23):7117-21 PMID: 6296817
  15. The transforming proteins of Rous sarcoma virus, Harvey sarcoma virus and Abelson virus contain tightly bound lipid.
    Cell. 1982 Dec;31(2 Pt 1):465-74 PMID: 6297767
  16. Interaction between the Rous sarcoma virus transforming protein and two cellular phosphoproteins: analysis of the turnover and distribution of this complex.
    Mol Cell Biol. 1983 Jan;3(1):9-19 PMID: 6298609
  17. Corrections to the nucleotide sequence of the src gene of Rous sarcoma virus.
    Nature. 1983 Feb 24;301(5902):736-8 PMID: 6298633
  18. Identification of a transformation-specific antigen induced by an avian sarcoma virus.
    Nature. 1977 Sep 22;269(5626):346-8 PMID: 198667
  19. Recovery of avian sarcoma virus from tumors induced by transformation-defective mutants.
    J Exp Med. 1977 Dec 1;146(6):1735-47 PMID: 200700
  20. Protein kinase activity associated with the avian sarcoma virus src gene product.
    Proc Natl Acad Sci U S A. 1978 Apr;75(4):2021-4 PMID: 205879
  21. Evidence that the transforming gene of avian sarcoma virus encodes a protein kinase associated with a phosphoprotein.
    Cell. 1978 Oct;15(2):561-72 PMID: 214242
  22. Characterization of a normal avian cell protein related to the avian sarcoma virus transforming gene product.
    Cell. 1978 Dec;15(4):1363-9 PMID: 83198
  23. Structural analysis of the avian sarcoma virus transforming protein: sites of phosphorylation.
    J Virol. 1979 Feb;29(2):770-81 PMID: 219258
  24. Uninfected vertebrate cells contain a protein that is closely related to the product of the avian sarcoma virus transforming gene (src).
    Proc Natl Acad Sci U S A. 1979 Apr;76(4):1804-8 PMID: 221907
  25. Cellular information in the genome of recovered avian sarcoma virus directs the synthesis of transforming protein.
    Proc Natl Acad Sci U S A. 1979 Jul;76(7):3154-8 PMID: 226955
  26. Evidence that the avian sarcoma virus transforming gene product is a cyclic AMP-independent protein kinase.
    Proc Natl Acad Sci U S A. 1979 Dec;76(12):6260-4 PMID: 230504
  27. Avian sarcoma virus-transforming protein, pp60src shows protein kinase activity specific for tyrosine.
    Nature. 1980 May 15;285(5761):167-9 PMID: 6246443
  28. Transforming gene product of Rous sarcoma virus phosphorylates tyrosine.
    Proc Natl Acad Sci U S A. 1980 Mar;77(3):1311-5 PMID: 6246487
  29. Evidence that the phosphorylation of tyrosine is essential for cellular transformation by Rous sarcoma virus.
    Cell. 1980 Jul;20(3):807-16 PMID: 6251974
  30. The protein encoded by the transforming gene of avian sarcoma virus (pp60src) and a homologous protein in normal cells (pp60proto-src) are associated with the plasma membrane.
    Proc Natl Acad Sci U S A. 1980 Jul;77(7):3783-7 PMID: 6253989
  31. Identification of a cellular protein substrate phosphorylated by the avian sarcoma virus-transforming gene product.
    Cell. 1980 Oct;21(3):829-36 PMID: 6254669
  32. Only membrane-associated RSV src proteins have amino-terminally bound lipid.
    Nature. 1983 Mar 10;302(5904):161-3 PMID: 6298640
  33. Structure and sequence of the cellular gene homologous to the RSV src gene and the mechanism for generating the transforming virus.
    Cell. 1983 Mar;32(3):881-90 PMID: 6299580
  34. Phosphorylation of tyrosine-416 is not required for the transforming properties and kinase activity of pp60v-src.
    Cell. 1983 Mar;32(3):891-901 PMID: 6403250
  35. 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
  36. Neural tissues express high levels of the cellular src gene product pp60c-src.
    Mol Cell Biol. 1983 Jun;3(6):1157-62 PMID: 6192323
  37. Local mutagenesis of Rous sarcoma virus: the major sites of tyrosine and serine phosphorylation of pp60src are dispensable for transformation.
    Cell. 1983 Sep;34(2):597-607 PMID: 6311433
  38. Isolation of monoclonal antibodies that recognize the transforming proteins of avian sarcoma viruses.
    J Virol. 1983 Nov;48(2):352-60 PMID: 6312092
  39. The erbB gene of avian erythroblastosis virus is a member of the src gene family.
    Cell. 1983 Nov;35(1):71-8 PMID: 6313229
  40. pp60c-src is developmentally regulated in the neural retina.
    Cell. 1984 Feb;36(2):249-57 PMID: 6198092
  41. Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences.
    Nature. 1984 Feb 9-15;307(5951):521-7 PMID: 6320011
  42. Subcellular localization of pp60src in RSV-transformed cells.
    Curr Top Microbiol Immunol. 1983;107:51-124 PMID: 6321110
  43. Expression of v-src and chicken c-src in rat cells demonstrates qualitative differences between pp60v-src and pp60c-src.
    Cell. 1984 May;37(1):131-9 PMID: 6426802
  44. Growth factors: mechanism of action and relation to oncogenes.
    Cell. 1984 May;37(1):9-20 PMID: 6373015
  45. Tyrosyl and cyclic AMP-dependent protein kinase activities in BHK cells that express viral pp60src.
    Mol Cell Biol. 1984 May;4(5):973-7 PMID: 6328280
  46. Identification, purification, and characterization of phosphotyrosine-specific protein phosphatases from cultured chicken embryo fibroblasts.
    Mol Cell Biol. 1984 Jun;4(6):1003-12 PMID: 6330524
  47. 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
  48. Rous sarcoma virus variants that carry the cellular src gene instead of the viral src gene cannot transform chicken embryo fibroblasts.
    Proc Natl Acad Sci U S A. 1984 Jul;81(14):4424-8 PMID: 6087323
  49. 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
  50. A short sequence in the p60src N terminus is required for p60src myristylation and membrane association and for cell transformation.
    Mol Cell Biol. 1984 Sep;4(9):1834-42 PMID: 6092942
  51. Structurally and functionally modified forms of pp60v-src in Rous sarcoma virus-transformed cell lysates.
    Mol Cell Biol. 1984 Jul;4(7):1213-20 PMID: 6095053
  52. Amino terminal myristylation of the protein kinase p60src, a retroviral transforming protein.
    Science. 1985 Jan 25;227(4685):427-9 PMID: 3917576
  53. Activation of the c-abl oncogene by viral transduction or chromosomal translocation generates altered c-abl proteins with similar in vitro kinase properties.
    Mol Cell Biol. 1985 Jan;5(1):204-13 PMID: 4039028
  54. Changes in protein phosphorylation in Rous sarcoma virus-transformed chicken embryo cells.
    Mol Cell Biol. 1981 Feb;1(2):165-78 PMID: 6100962
  55. Viral and cellular src genes contribute to the structure of recovered avian sarcoma virus transforming protein.
    Cell. 1981 Apr;24(1):155-64 PMID: 6263484
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
Published
1985-05-00
Pages
1058-66
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC366822
Subset
IM
Grants
NIAID NIH HHS · AI07233 · United States
NCI NIH HHS · CA14935 · United States
NCI NIH HHS · CA18213 · United States
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com