Retroviruses 2 pp 163-180 | Cite as

Phosphotyrosyl-Protein Phosphatases

  • J. Gordon Foulkes
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 107)


Extensive genetic evidence indicates that the protein product of a single gene of RNA tumor viruses is responsible for the transformation of virus-infected cells to the malignant state (Hanafusa 1977; Duesberg and Bister 1981; Bishop and Varmus 1982; Linial and Blair 1982; Varmus 1982).


Phosphatase Activity Protein Phosphatase Glycogen Metabolism Rous Sarcoma Virus Ehrlich Ascites Tumor Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Ambros V, Baltimore D (1978) Protein is linked to the 5’ end of polio virus RNA by a phosphodiester linkage to tyrosine. J Biol Chem 253: 5263–5266PubMedGoogle Scholar
  2. Antoniw JF, Cohen P (1976) Separation of two phosphorylase kinase phosphatases from rabbit skeletal muscle. Eur J Biochem 68: 45–54CrossRefPubMedGoogle Scholar
  3. Avruch J, Nemenoff A, Blackshear PJ, Pierce MW, Osathanondh R (1982) Insulin–stimulated tyrosine phosphorylation of the insulin receptor in detergent extracts of human placental membranes. J Biol Chem 257: 15162–15166PubMedGoogle Scholar
  4. Beemon K (1981) Transforming proteins of some feline and avian sarcoma viruses are related structurally and functionally. Cell 24: 145–153CrossRefPubMedGoogle Scholar
  5. Bishop MJ (1982) Oncogenes. Sci Am 246: 80–93PubMedGoogle Scholar
  6. Bishop JM, Varmus H (1982) Functions and origins of retroviral transforming genes. In: Weiss R, Teich N, Varmus H, Coffin J (eds) RNA tumor viruses, 2nd edn. Cold Spring Harbor Laboratory, New York, pp 999–1108Google Scholar
  7. Brautigan DL, Bornstein P, Gallis B (1981) Phosphotyrosyl-protein phosphatases. J Biol Chem 256: 6519–6522PubMedGoogle Scholar
  8. Buhrow SA, Cohen S, Staros JY (1982) Affinity labeling of the protein kinase associated with epidermal growth factor receptor in membrane vesicles from A431 cells. J Biol Chem 257: 4019–4022PubMedGoogle Scholar
  9. Carpenter G, King L, Cohen S (1979) Rapid enhancement of protein phosphorylation in A-431 cell membrane preparations by epidermal growth factor. J Biol Chem 254: 4884–4891PubMedGoogle Scholar
  10. Cheraoff J, Li HC (1983) Multiple forms of phosphotyrosyl-protein phosphatase from bovine heart and brain. Fed Am Soc Exp Biol (in press)Google Scholar
  11. Chernoff J, Li HC, Cheng YS, Chen LB (1983) Characterisation of a phosphotyrosyl-protein phosphatase activity associated with a phosphoseryl-protein phosphatase of Mr = 95000 from bovine heart. J Biol Chem (in press)Google Scholar
  12. Chernoff J, Tabarini D, Li HC, Cheng YSE, Chen LB (to be published) Dephosphorylation of phosphotyrosyl-protein by type II phosphoprotein phosphatase.Google Scholar
  13. Cohen P (1978) The role of the cyclic AMP dependent protein kinase in the regulation of glycogen metabolism in mammalian skeletal muscle. Curr Top Cell Regul 14: 118–196Google Scholar
  14. Cohen P (ed) (1980) Recently discovered systems of enzyme regulation by reversible phosphorylation. In: Molecular aspects of cellular regulation, vol 1. Elsevier/North-Holland, New YorkGoogle Scholar
  15. Cohen P (1982) The role of protein phosphorylation in neural and hormonal control of cellular activity. Nature 296: 613–619CrossRefPubMedGoogle Scholar
  16. Cohen P, Foulkes JG, Goris J, Hemmings BA, Ingebritsen TS, Stewart AA, Strada ST (1981) Classification of protein phosphatases involved in cellular regulation. In: Holzer H (ed) Metabolic interconversion of enzymes 1980. Springer, Berlin Heidelberg New YorkGoogle Scholar
  17. Collett MS, Erikson E, Purchio AF, Brugge JS, Erikson RL (1979) A normal cell protein similar in structure and function to the avian sarcoma virus transforming gene product. Proc Natl Acad Sci USA 76: 3159–3163CrossRefPubMedPubMedCentralGoogle Scholar
  18. Cooper JA, Hunter T (1981) Changes in protein phosphorylation in Rous sarcoma virus transformed chicken embryo cells. Mol Cell Biol 1: 165–178CrossRefPubMedPubMedCentralGoogle Scholar
  19. Cooper JA, Hunter T (1983) Identification and characterisation of cellular targets for tyrosine protein kinases. J Biol Chem 258: 1108–1115PubMedGoogle Scholar
  20. Cooper JA, Bowen-Pope DF, Raines E, Ross R, Hunter T (1982) Similar effects of platelet derived growth factor and epidermal growth factor on phosphorylation of tyrosine in cellular proteins. Cell 31: 263–273CrossRefPubMedGoogle Scholar
  21. Cooper JA, Reiss NA, Schwartz RJ, Hunter T (1983) Three glycolytic enzymes are phosphorylated at tyrosine in cells transformed by Rous sarcoma virus. Nature 302: 218–223CrossRefPubMedGoogle Scholar
  22. Crouch D, Safer B (1980) Purification and properties of elF-2 phosphatase. J Biol Chem 255: 7918–7924PubMedGoogle Scholar
  23. Curnow RT, Larner J (1979) Hormonal and metabolic control of phosphoprotein phosphatase. In: Litwack G (ed) Biochemical actions of hormones, vol 6. Academic, New York, pp 77–119CrossRefGoogle Scholar
  24. Duesberg PM, Bister K (1981) Transforming genes of retroviruses. Cancer 1: 111–136Google Scholar
  25. Eckhart W, Hutchinson MA, Hunter T (1979) An activity phosphorylating tyrosine in polyoma T antigen immunoprecipitates. Cell 18: 925–933CrossRefPubMedGoogle Scholar
  26. Ek B, Heldin CH (1982) Characterization of a tyrosine specific kinase activity in human fibroblast membranes stimulated by platelet–derived growth factor. J Biol Chem 257: 10486–10492PubMedGoogle Scholar
  27. Ek B, Westermark B, Wasteson A, Heldin CH (1982) Stimulation of tyrosine-speciflc phosphorylation by platelet-derived growth factor. Nature 295: 419–420CrossRefPubMedGoogle Scholar
  28. Erikson RL, Purchio AF, Erikson E, Collett MS, Brugge JS (1980) Molecular events in cells transformed by Rous sarcoma virus. J Cell Biol 87: 319–325CrossRefPubMedGoogle Scholar
  29. Erikson E, Cook R, Miller GJ, Erikson RL (1981) The same normal cell protein is phosphorylated after transformation by avian sarcoma viruses with unrelated transforming genes. Mol Cell Biol 1: 43–50CrossRefPubMedPubMedCentralGoogle Scholar
  30. Eva A, Robbins KC, Andersen PR, Srinivasan A, Tronick SR, Reddy EP, Ellmore NW, Galen AT, Lautenberger JA, Papas TS, Westin EH, Wong-Staal F, Gallo RC, Aaronson SA (1982) Cellular genes analogous to retroviral one genes are transcribed in human tumor cells. Nature 295: 116–119CrossRefPubMedGoogle Scholar
  31. Fernley HN (1971) Mammalian alkaline phosphatases. In: Boyer PD (ed), The enzymes, vol 4, 3rd edn, Academic, New York, pp 417–447Google Scholar
  32. Foulkes JG, Cohen P (1979) Hormonal control of glycogen metabolism. Eur J Biochem 97: 251–256CrossRefPubMedGoogle Scholar
  33. Foulkes JG, Cohen P (1980) Regulation of glycogen metabolism. Eur J Biochem 105:195–203 Foulkes JG, Mailer JL (1982) In vivo actions of protein phosphatase inhibitor-2 in Xenopus oocytes. FEBS Lett 150: 155–160Google Scholar
  34. Foulkes JG, Howard RF, Ziemiecki A (1981) Detection of a novel mammalian protein phosphatase with activity for phosphotyrosine. FEBS Lett 130: 197–200CrossRefPubMedGoogle Scholar
  35. Foulkes JG, Cohen P, Strada S, Everson WY, Jefferson LS (1982) Antagonistic effects of insulin and -adrenergic agonists on the activity of protein phosphatase inhibitor-1 in skeletal muscle of the perfused rat hemicorpus. J Biol Chem 257: 12493–12496PubMedGoogle Scholar
  36. Foulkes JG, Erikson E, Erikson RL (1983 a) Separation of multiple phosphotyrosyl-protein phosphatases from chicken brain. J Biol Chem 258: 431–438Google Scholar
  37. Foulkes JG, Ernst V, Levin DH (1983 b) Separation and identification of type 1 and type 2 protein phosphatases from rabbit reticulocyte lysates. J Biol Chem 258: 1439–1443Google Scholar
  38. Friis RR, Jockusch BM, Boschek CB, Ziemiecki A, Rusamen H, Bauer H (1979) Transformation-defective, temperature sensitive mutants of Rous sarcoma virus have a reversibly defective sregene product. Cold Spring Harbor Symp Quant Biol 44: 1007–1012CrossRefGoogle Scholar
  39. Fukami Y, Lipmann F (1982) Purification of a specific reversible tyrosine-O-phosphate phosphatase. Proc Natl Acad Sci USA 79: 4275–4279CrossRefPubMedPubMedCentralGoogle Scholar
  40. Fukami Y, Lipmann F (1983) Reversal of Rous sarcoma-specific immunoglobulin phosphoryla-tion on tyrosine ( ADP as phosphate acceptor) catalysed by the sre gene kinase. Proc Natl Acad Sci USA 80: 1872–1876Google Scholar
  41. Gallis B, Bornstein P, Brautigan DL (1981) Tyrosylprotein kinase and phosphatase activities in membrane vesicles from normal and Rous sarcoma virus–transformed rat cells. Proc Natl Acad Sci USA 78: 6689–6693CrossRefPubMedPubMedCentralGoogle Scholar
  42. Goyette M, Petropoulos CJ, Shank PR, Fausto N (1983) Expression of a cellular oncogene during liver regeneration. Science 219: 510–512CrossRefPubMedGoogle Scholar
  43. Green GA, Chenoweth M, Dunn A (1980) Adrenal glucocorticoid permissive regulation of muscle glycogenolysis. Proc Natl Acad Sci USA 77: 5711–5715CrossRefPubMedPubMedCentralGoogle Scholar
  44. Hanafusa H (1977) Cell transformation by RNA tumor viruses. Compr Virol 10:401–481 Hemmings BA, Yellowlees D, Kernohan JC, Cohen P (1981) Purification of glycogen synthase kinase-3 from rabbit skeletal muscle. Eur J Biochem 119: 443–451Google Scholar
  45. Hemmings BA, Resink T, Cohen P (1982) Reconstruction of a MgATP dependent phosphatase and its activation through a phosphorylation mechanism. FEBS Lett 150: 319–324CrossRefPubMedGoogle Scholar
  46. Hoffman-Falk H, Einat P, Shilo B, Hoffman FM (1983) Drosophila melanogaster DNA clones homologous to vertebrate oncogenes. Cell 32: 589–598CrossRefPubMedGoogle Scholar
  47. Horlein D, Gallis B, Brautigan DL, Bornstein P (1982) Partial purification and characterization of phosphotyrosyl-protein phosphatase from Ehrlich ascites tumor cells. Biochemistry 21: 5577–5584CrossRefPubMedGoogle Scholar
  48. Hunter T, Sefton BM (1981) Protein kinases and viral transformation. In: Cohen P, Van Heyningen S (eds) Molecular aspects of cellular regulation, vol 2. Elsevier-North Holland, New York, pp 337–370Google Scholar
  49. Hunter T, Sefton BM, Beemon K (1979) Studies on the structure and function of the avian sarcoma virus transforming gene product. Cold Spring Harbor Symp Quant Biol 44: 931–941CrossRefGoogle Scholar
  50. Ingebritsen TS, Foulkes JG, Cohen P (1980) The broad specificity protein phosphatase from mammalian liver. FEBS Lett 119: 9–15CrossRefPubMedGoogle Scholar
  51. Ingebritsen TS, Foulkes JG, Cohen P (1983 a) Classification of protein phosphatases involved in the regulation of glycogen metabolism. Eur J Biochem 132: 263–274Google Scholar
  52. Ingebritsen TS, Stewart AA, Cohen P (1983 b) Measurement of type 1 and type 2 protein phosphatases in extracts of mammalian tissues. Eur J Biochem 132: 297–307Google Scholar
  53. Kasuga M, Zick Y, Blithe DL, Crettaz M, Kahn CR (1982 a) Insulin stimulates tyrosine phosphorylation of the insulin receptor in a cell–free system. Nature 228: 667–669Google Scholar
  54. Kasuga M, Zick Y, Blith DL, Karlsson FA, Haring HU, Kahn CR (1982b) Insulin stimulation of phosphorylation of the subunit of the insulin receptor. J Biol Chem 257: 9891–9894PubMedGoogle Scholar
  55. Krebs EG, Beavo JA (1979) Phosphorylation-dephosphorylation of enzymes. Annu Rev Biochem 48: 923–959CrossRefPubMedGoogle Scholar
  56. Lee EYC, Silberman SR, Ganapathi MK, Petrovic S, Paris H (1980) The phosphoprotein phosphatases. Adv Cyclic Nucleotide Res 13: 95–131PubMedGoogle Scholar
  57. Lee EYC, Silberman SR, Ganapathi MK, Paris H, Petrovic S (1981) Properties of rabbit skeletal muscle protein phosphatases. In: Rosen OM, Krebs EG (eds) Cold Spring Harbor conferences on cell proliferation, vol 8. Cold Spring Harbor, New York, pp 425–439Google Scholar
  58. Lee W, Bister K, Moscovici C, Duesberg P (1981) Temperature-sensitive mutants of Fujinami sarcoma virus. J Virol 38: 1064–1076PubMedPubMedCentralGoogle Scholar
  59. Leis JF, Kaplan NO (1982) An acid phosphatase in the plasma membranes of human astrocytoma showing marked specificity toward phosphotyrosine protein. Proc Natl Acad Sci USA 79; 6507–6511CrossRefPubMedPubMedCentralGoogle Scholar
  60. Li HC (1981) Purification and properties of cardiac muscle phosphoprotein phosphatase and alkaline phosphatase isoenzymes. In: Rosen OM, Krebs EG (eds) Cold Spring Harbor conferences on cell proliferation, vol 8. Cold Spring Harbor, New York, pp 441–457Google Scholar
  61. Li HC (1982) Phosphoprotein phosphatases. Curr Top Cell Regul 21: 129–173CrossRefPubMedGoogle Scholar
  62. Li HC, Hsiao KJ, Chan WWS (1978) Purification and properties of phosphoprotein phosphatases from canine heart. Eur J Biochem 84: 215–225CrossRefPubMedGoogle Scholar
  63. Li HC, Tabarini D, Cheng YS, Chen LB (1981) Dephosphorylation of pp60src-protein kinase phosphorylated immunoglobulin by type II phosphoprotein phosphatase. Fed Am Soc Exp Biol 40: 1539 (Abstr 5)Google Scholar
  64. Linial M, Blair D (1982) Genetics of retroviruses. In: Weiss R, Teich N, Varmus H, Coffin J (eds) RNA tumor viruses, 2nd edn. Cold Spring Harbor Laboratory, New York, pp 649–784Google Scholar
  65. Manning DR, DiSalvo J, Stull JT (1980) Protein phosphorylation: quantitative analysis in vivo and in intact cell systems. Mol Cell Endocrinol 19: 1–19CrossRefPubMedGoogle Scholar
  66. Mitchell HK, Lunan KD (1964) Tyrosine-O-phosphate in Drosophila. Arch Biochem Biophys 106: 219–222CrossRefPubMedGoogle Scholar
  67. Muller R, Slamon DJ, Tremblay JM, Cline MJ, Verma IM (1982) Differential expression of cellular oncogenes during pre– and post–natal development of the mouse. Nature 299: 640–644CrossRefPubMedGoogle Scholar
  68. Nimmo GA, Cohen P (1978 a) Regulation of glycogen metabolism. Eur J Biochem 87: 341–351Google Scholar
  69. Nimmo GA, Cohen P (1978 b) Regulation of glycogen metabolism. Eur J Biochem 87: 353–365Google Scholar
  70. Nimmo HG, Cohen P (1977) Hormonal control of protein phosphorylation. Adv Cyclic Nuceotide Res 8: 146–260Google Scholar
  71. Pato M, Adelstein RS (1980) Dephosphorylation of the 20000 dalton light chain of myosin by two different phosphatases from smooth muscle. J Biol Chem 255: 6535–6538PubMedGoogle Scholar
  72. Pato M, Adelstein RS, Crouch DB, Safer B, Ingebritsen TS, Cohen P (1983) Classification of two homogeneous myosin light chain phosphatases and a homogeneous protein phosphatase from reticulocytes. Eur J Biochem 132: 283–287CrossRefPubMedGoogle Scholar
  73. Radke K, Martin GS (1979) Transformation by Rous sarcoma virus: effects of srcgene expression on the synthesis and phosphorylation of cellular polypeptides. Cold Spring Harbor Symp Quant Biol 44: 975–982CrossRefGoogle Scholar
  74. Radke K, Gilmore T, Martin GS (1980) Transformation by Rous sarcoma virus: a cellular substrate for transformation-specific protein phosphorylation contains phosphotyrosine. Cell 21: 821–828CrossRefPubMedGoogle Scholar
  75. Resink T, Hemmings BA, Lim Tung HY, Cohen P (1983) Characterisation of a reconstituted MgATP dependent protein phosphatase. Eur J Biochem 133: 455–461CrossRefPubMedGoogle Scholar
  76. Reynolds FH, Todaro GJ, Fryling C, Stephenson JR (1981) Human transforming growth factors induce tyrosine phosphorylation of EGF receptor. Nature 292: 259–262CrossRefPubMedGoogle Scholar
  77. Rothberg PG, Harris TJR, Nomoto A, Wimmer E (1978) 04-(5/-uridylyl) tyrosine is the bond between the genome-linked protein and the RNA of poliovirus. Proc Natl Acad Sci USA 75: 4868–4872Google Scholar
  78. Schartl M, Barnekow A (1982) Expression in eukaryotes of a tyrosine kinase which is reactive with pp60vsrc antibodies. Differentiation 23: 109–114CrossRefPubMedGoogle Scholar
  79. Sefton BM, Hunter T, Beeman K, Eckhart W (1980) Evidence that the phosphorylation of tyrosine is essential for cellular transformation by Rous sarcoma virus. Cell 20: 807–816CrossRefPubMedGoogle Scholar
  80. Sefton BM, Hunter T, Ball EH, Singer SJ (1981) Vinculin: a cytoskeletal target of the transforming protein of Rous sarcoma virus. Cell 24: 165–174CrossRefPubMedGoogle Scholar
  81. Shapiro BM, Stadtman ER (1968) S’Adenylyl-O-tyrosine. J Biol Chem 243: 3769–3771PubMedGoogle Scholar
  82. Shizuta Y, Beavo J A, Bechtel PJ, Hoffmann F, Krebs EG (1975) Reversibility of adenosine 3-5 monophosphate dependent protein kinase reactions. J Biol Chem 250: 6891–6896PubMedGoogle Scholar
  83. Shizuta Y, Khandelwal RJ, Mailer JL, Van Den Heede JR, Krebs EG (1977) Reversibility of phosphorylase kinase reaction. J Biol Chem 252: 3408–3413PubMedGoogle Scholar
  84. Spector DH, Varmus HE, Bishop JM (1978) Nucleotide sequences related to the transforming gene of avian sarcoma virus are present in DNA of uninfected vertebrates. Proc Natl Acad Sci USA 75: 4102–4106CrossRefPubMedPubMedCentralGoogle Scholar
  85. Stewart AA, Hemmings BA, Cohen P, Goris J, Merlevede W (1981) The MgATP–dependent protein phosphatase and protein phosphatase–1 have identical substrate specificities. Eur J Biochem 115: 197–205CrossRefPubMedGoogle Scholar
  86. Stewart AA, Ingebritsen TS, Manalan A, Klee CB, Cohen P (1982) Discovery of a Ca+ + and calmodulin-dependent protein phosphatase. FEBS Lett 137: 80–84CrossRefPubMedGoogle Scholar
  87. Stewart AA, Ingebritsen TS, Cohen P (1983) Purification and properties of a calcium ion and calmodulin dependent protein phosphatase 2B from rabbit skeletal muscle. Eur J Biochem 132: 289–295CrossRefPubMedGoogle Scholar
  88. Swarup G, Cohen S, Garbers DL (1981) Selective dephosphorylation of proteins containing phosphotyrosine by alkaline phosphatases. J Biol Chem 256: 8197–8201PubMedGoogle Scholar
  89. Swarup G, Cohen S, Garbers DL (1982 a) Inhibition of phosphotyrosyl-protein phosphatase activity by vanadate. Biochem Biophys Res Commun 107: 1104–1109Google Scholar
  90. Swarup G, Speeg KV, Cohen S, Garbers DL (1982 b) Phosphotyrosyl-protein phosphatase of TCRC-2 cells. J Biol Chem 257: 7298–7301Google Scholar
  91. Taborsky G (1974) Phosphoproteins. Adv Protein Chem 28: 1–210CrossRefPubMedGoogle Scholar
  92. Tamura S, Tsuiki S (1980) Purification and subunit structure of rat-liver phosphoprotein phosphatase Mt = 260000. Eur J Biochem 111: 217–224CrossRefPubMedGoogle Scholar
  93. Tamura S, Kikuchi H, Kikuchi K, Hiraga A, Tsuiki S (1980) Purification and subunit structure of rat liver phosphoprotein phosphatase II. Eur J Biochem 104: 347–355CrossRefPubMedGoogle Scholar
  94. Ushiro H, Cohen S (1980) Identification of phosphotyrosine as a product of epidermal growth factor-activated protein kinase in A431 cell membranes. J Biol Chem 255: 8363–8365PubMedGoogle Scholar
  95. Vandenheede JR, Yang SD, Goris J, Merlevede W (1980) ATPMg dependent protein phosphatase from rabbit skeletal muscle. J Biol Chem 255: 11768–11774PubMedGoogle Scholar
  96. Vandenheede JR, Goris J, Yang SD, Camps T, Merlevede W (1981a) Conversion of active protein phosphatase to the ATPMg-dependent form enzyme by inhibitor-2. FEBS Lett 127: 1–3CrossRefPubMedGoogle Scholar
  97. Vandenheede JR, Yang SD, Merlevede W (1981 b) Rabbit skeletal muscle protein phosphatase. J Biol Chem 256: 5894–5900Google Scholar
  98. Varmus HE (1982) Form and function of retroviral proviruses. Science 216: 812–820CrossRefPubMedGoogle Scholar
  99. Walsh DA, Perkins JP, Krebs EG (1968) An adenosine 2/,5,-monophosphate dependent protein kinase from rabbit skeletal muscle. J Biol Chem 243: 3763–3765PubMedGoogle Scholar
  100. Weller M (1979) Protein phosphorylation. In: Lagnado JR (ed) Pion, LondonGoogle Scholar
  101. Witte O, Dasgupta A, Baltimore D (1980) Abelson murine leukaemia virus protein is phosphorylated in vitro to form phosphotyrosine. Nature 283: 826–831CrossRefPubMedGoogle Scholar
  102. Yang SD, Vandenheede JR, Goris J, Merlevede W (1980) ATPMg dependent protein phosphatase from rabbit skeletal muscle. J Biol Chem 255: 11759–11767PubMedGoogle Scholar
  103. Zick Y, Kasuga M, Kahn RC, Roth J (1983) Characterization of insulin mediated phosphorylation of the insulin receptor in a cell-free system. J Biol Chem 258: 75–80PubMedGoogle Scholar
  104. Ziemiecki A, Friis RR (1980) Phosphorylation of pp60src and the cyclohexamide insensitive activation of the pp60src associated kinase activity of transformation-defective temperature-sensitive mutants of Rous sarcoma virus. Virology 106: 391–394CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin · Heidelberg 1983

Authors and Affiliations

  • J. Gordon Foulkes
    • 1
  1. 1.Center for Cancer ResearchMassachusetts Institute of TechnologyCambridgeUSA

Personalised recommendations