Vanadium salts stimulate mitogen-activated protein (MAP) kinases and ribosomal S6 kinases

  • Sanjay K. Pandey
  • Jean-Louis Chiasson
  • Ashok K. Srivastava
Part of the Developments in Molecular and Cellular Biochemistry book series (DMCB, volume 16)


Effect of several vanadium salts, sodium ortho vanadate, vanadyl sulfate and sodium meta vanadate on protein tyrosine phosphorylation and serine/threonine kinases in Chinese hamster ovary (CHO) cells overexpressing a normal human insulin receptor was examined. All the compounds stimulated protein tyrosine phosphorylation of two major proteins with molecular masses of 42 kDa (p42) and 44 kDa (p44). The phosphorylation of p42 and p44 was associated with an activation of mitogen activated protein (MAP) kinase as well as increased protein tyrosine phosphorylation of p42mapk and p44mapk. Vanadium salts also activated the 90 kDa ribosomal s6 kinase (p90rsk) and 70 kDa ribosomal s6 kinase (p70s6k). Among the three vanadium salts tested, vanadyl sulfate appeared to be slightly more potent than others in stimulating MAP kinases and p70s6k activity. It is suggested that vanadium-induced activation of MAP kinases and ribosomal s6 kinases may be one of the mechanisms by which insulin like effects of this trace element are mediated.

Key words

vanadium salts MAP kinase ribosomal s6 kinases (p90rsk andp70s6kinsulinomimesis protein tyrosine phosphatase 



eukaryotic protein synthesis initiation factor-4


growth factor receptor bound protein-2


Glycogen Synthase Kinase-3


insulin receptor substrate-1


insulin stimulated protein kinase


mitogen activated protein kinase, also known as: ERK — extracellular signal regulated kinase


mitogen activated protein kinase kinase, also known as —MEK, MAPK or ERK kinase


phosphorylated heat and acid stable protein regulated by insulin


phosphatidyl inositol 3-kinase


protein phosphatase-glycogen bound form


protein tyrosine kinase


protein tyrosine phosphatase


ribosomal s6 kinases


src homology domain containing protein


son of sevenless


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Ramasarma T, Crane FL: Does vanadium play a role in cellular regulation? Curr Topics Cell Regul 20: 247–301, 1991Google Scholar
  2. 2.
    Chasteen ND: The biochemistry of vanadium. In: Structure and bonding 53. Springer Verlag, Beding, Heidelberg, 1983, pp 105–138Google Scholar
  3. 3.
    Nechay BR: Mechanisms of action of vanadium. Ann Rev Pharmacol Toxicol 24: 501–524, 1984CrossRefGoogle Scholar
  4. 4.
    Tolman EL, Barris E, Burns M, Pansini A, Partridge R: Effects of vanadium on glucose metabolism in vitro. Life Sci 25: 1159—1164, 1979Google Scholar
  5. 5.
    Shechter Y, Karlish SJD: Insulin-like stimulation of glucose oxidation in rat adipocytes by vanadyl (IV) ions. Nature 284: 556–558, 1980PubMedCrossRefGoogle Scholar
  6. 6.
    Dubyak GR, Kleinzeller A: The insulin-mimetic effects of vanadate as (Na+, K+) ATPase inhibitor. J Biol Chem 255: 5306–5312, 1980PubMedGoogle Scholar
  7. 7.
    Singh J, Nordlis RC, Jorgenson RA: Vanadate: a potent inhibitor of multifunctional glucose-6-phosphatase. Biochem Biophys Acta 678: 477–482, 1981PubMedGoogle Scholar
  8. 8.
    Degani H, Gochin M, Karlish SJO, Shechter Y: Electron paramagnetic resonance studies and insulin-like effects of vanadium in rat adipocytes. Biochem 20: 5795–5799, 1981CrossRefGoogle Scholar
  9. 9.
    Carpenter G: Vanadate, epidermal growth factor and the stimulation of DNA synthesis. Biochem Biophys Res Commun 102: 1115–1121, 1982CrossRefGoogle Scholar
  10. 10.
    Smith JB: Vanadium ions stimulated DNA synthesis in Swiss mouse 3T3 and 3T6 cells. Proc Natl Acad Sci USA 80: 6162–6166, 1983PubMedCrossRefGoogle Scholar
  11. 11.
    Tamura S, Brown TA, Whipple JH, Yamaguchi YF, Dubler RE, Chen K, Larner J: A novel mechanism of the insulin-like effects of vanadate on glycogen synthase in rat adipocytes. J Biol Chem 259: 6650–6658, 1984PubMedGoogle Scholar
  12. 12.
    Clark AS, Fagan JM, Mitch WE: Selectivity of the insulin-like actions of vanadate on glucose and protein metabolism in skeletal muscle. Biochem J 232: 273–276, 1985PubMedGoogle Scholar
  13. 13.
    Klarlund JR: Transformation of cells by an inhibitor of phosphatases acting on phosphotyrosine in proteins. Cell 41: 707–717, 1985PubMedCrossRefGoogle Scholar
  14. 14.
    Green A: The insulin like effect of sodium vanadate on adipocyte glucose transport is mediated at a post-insulin-receptor level. Biochem J 238: 663–669, 1986PubMedGoogle Scholar
  15. 15.
    Bosch F, Arino J, Gomez-Foix AM, Guinovart JJ: Glycogenolytic noninsulin-like effects of vanadate on rat hepatocyte glycogen synthase and Phosphorylase. J Biol Chem 262: 218–222, 1987PubMedGoogle Scholar
  16. 16.
    Gomez-Foix AM, Rodriguez-Gil JE, Fillat C, Guinovart JJ, Boxch F: Vanadate raises fructose 2,6-bisphosphate concentrations and activates glycolysis in rat hepatocytes. Biochem J 255: 507–512, 1988PubMedGoogle Scholar
  17. 17.
    Jackson TK, Salhanick AI, Sparks JD, Sparks CE, Bolognino M, Amatruda JM: Insulin mimetic effects of vanadate in primary cultures of rat hepatocytes. Diabetes 37: 1234–1240, 1988PubMedCrossRefGoogle Scholar
  18. 18.
    Duckworth WC, Solomon SS, Liepnicks SJ, Hamel FG, Hand S, Peaw DE: Insulin-like effects of vanadate in isolated rat adipocytes. Endocrinology (1988) 122: 2285–2289, 1988Google Scholar
  19. 19.
    Fantus IG, Kadota SI, Deragon G, Foster B, Posner BI: Pervanadate (peroxide(s) of vanadate) mimics insulin action in rat adipocytes via activation of the insulin receptor tyrosine kinase. Biochemistry 28: 8864–8871, 1989PubMedCrossRefGoogle Scholar
  20. 20.
    Rodriguez-Gil JE, Gomez-Foix AM, Arino J, Guniovart J J, Bosch F: Control of glycogen synthase and Phosphorylase in hepatocytes from diabetic rats. Diabetes 38: 793–798, 1989PubMedCrossRefGoogle Scholar
  21. 21.
    Miralpeix M, Gil J, Rosa JC, Carreras J, Bartrons R: Vanadate counteracts glucagon effects in isolated rat hepatocytes. Life Sci 44: 1491–1497, 1989PubMedCrossRefGoogle Scholar
  22. 22.
    Rider MH, Bartrons R, Hue L: Vanadate inhibits liver fructose-2,6-bisphosphatase. Eur J Biochem 209: 53–56, 1990CrossRefGoogle Scholar
  23. 23.
    Mountjoy KG, Flier JS: Vanadate regulates glucose transporter (Glut-1) expression in NIH 3T3 mouse fibroblasts. Endocrinology 26: 2778–2787, 1990CrossRefGoogle Scholar
  24. 24.
    Miralpeix M, Decaux JF, Kahn A, Bartrons R: Vanadate induction of L-type pyruvate kinase mRNA in adult rat hepatocytes in primary culture. Diabetes 40: 462–464, 1991PubMedCrossRefGoogle Scholar
  25. 25.
    Shechter Y: Insulin-mimetic effects of vanadate: Possible implications for future treatment of diabetes. Diabetes 39: 1–5, 1990PubMedCrossRefGoogle Scholar
  26. 26.
    Heyliger CE, Tahiliani AG, McNeill JH: Effect of vanadate on elevated blood glucose and depressed cardiac performance of diabetic rats. Science 277: 1474–1477, 1985CrossRefGoogle Scholar
  27. 27.
    Meyerovitch J, Farfel Z, Sack J, Shechter Y: Oral administration of vanadate normalizes blood glucose levels in streptozotocin-treated rats. J Biol Chem 262: 6658–6662, 1987PubMedGoogle Scholar
  28. 28.
    Brichard SM, Portier AM, Henquin JC: Long term improvement of glucose homeostasis by vanadate in obese hyperinsulinemic fa/fa rats. Endocrinology 125: 2510–2516, 1989PubMedCrossRefGoogle Scholar
  29. 29.
    Pugazhenthi S, Angel JF, Khandelwal RZ: Long-term effects of vanadate treatment on glycogen metabolizing and lipogenic enzymes of liver in genetically diabetic (db/db) mice. Metabolism 40: 941–946, 1991PubMedCrossRefGoogle Scholar
  30. 30.
    Meyerovitch J, Rothenberg P, Shechter Y, Bonner-Weir S, Kahn CR: Vanadate normalizes hyperglycemia in two mouse models of noninsulin-dependent diabetes mellitus. J Clin Invest 87: 1286–1294, 1991PubMedCrossRefGoogle Scholar
  31. 31.
    Gil J, Miralprix M, Carreras J, Bartrons R: Insulin-like effects of vanadate on glucokinase activity and fructose 2,6-biphosphate levels in the liver of diabetic rats. J Biol Chem 263: 1868–1871, 1988PubMedGoogle Scholar
  32. 32.
    Brichard SM, Okitolonda W, Henquin JC: Long term improvement of glucose homeostasis by vanadate treatment in diabetic rats. Endocrinology 123: 2048–2053, 1988PubMedCrossRefGoogle Scholar
  33. 33.
    Pugazhenthi S, Khandelwal RL: Insulinlike effects of vanadate on hepatic glycogen metabolism in nondiabetic and streptozotocin-in-duced diabetic rats. Diabetes 39: 821–827, 1990PubMedCrossRefGoogle Scholar
  34. 34.
    Rossetti L, Laughlin MR: Correction of chronic hyperglycemia with vanadate, but not with phlorizin, normalizes in vivo glycogen repletion and in vitro glycogen synthase activity in diabetic skeletal muscle. J Clin Invest 84: 892–899, 1989PubMedCrossRefGoogle Scholar
  35. 35.
    Bollen M, Miralpeix M, Ventura F, Toth B, Bartrons R, Stalmans W: Oral administration of vanadate to streptozotocin-diabetic rats restores the glucose-induced activation of liver glycogen synthase. Biochem J 267: 269–271, 1990PubMedGoogle Scholar
  36. 36.
    Strout HV, Vicario PP, Biswas C, Superstein R, Brady EJ, Pilch PF, Berger J: Vanadate treatment of streptozotocin diabetic rats restores expression of the insulin responsive glucose transporter in skeletal muscle. Endocrin 126: 2728–2732, 1990CrossRefGoogle Scholar
  37. 37.
    Sekar N, Kanthasamy A, William S, Subramanian S, Govindasamy S: Insulin actions of vanadate in diabetic rats. Pharmacol. Res. 22: 207–217, 1989CrossRefGoogle Scholar
  38. 38.
    Saxena AK, Srivastava P, Bacquer NZ: Effects of vanadate on glycolytic enzymes and malic enzyme in insulin-dependent and independent tissues of diabetic rats. Eur J Pharmacol 216: 123–126, 1992PubMedCrossRefGoogle Scholar
  39. 39.
    Valera A, Rodriguez-Gil JE, Bosch F: Vanadate treatment restores the expression of genes for key enzymes in the glucose and ketone bodies metabolism in the liver of diabetic rats. J Clin Invest 92: 4–11, 1993PubMedCrossRefGoogle Scholar
  40. 40.
    Brichard SM, Desbuquois B, Girard J: Vanadate treatment of diabetic rats reverses the impaired expression of genes involved in hepatic glucose metabolism: effects on glycolytic and gluconeogenic enzymes and on glucose transporter GLUT2. Mol Cell Endocrinol 91: 91–97, 1993PubMedCrossRefGoogle Scholar
  41. 41.
    Miralpeix M, Carballo E, Bartrons R, Crepin K, Hue L, Rousseau GG: Oral administration of vanadate to diabetic rats restores liver 6-phosphofructo-2-kinase content and mRNA. Diabetologia 35: 243–248, 1992PubMedCrossRefGoogle Scholar
  42. 42.
    Pugazhenthi S, Khandelwal RL, Angel JF: Insulin like effects of vanadate on malic enzyme and glucose-6-phosphate dehydrogenase activites in streptozotocin-induced diabetic rat liver. Biochim Biophys Acta 1083: 310–312, 1991PubMedGoogle Scholar
  43. 43.
    Brichard SM, Ongemba LN, Girard J, Henquin JC: Tissue specific correction of lipogenic enzyme gene expression in diabetic rats given vanadate. Diabetologia 37: 1065–1072, 1994PubMedCrossRefGoogle Scholar
  44. 44.
    Srivastava AK: Potential use of vanadium compounds in the treatment of diabetes mellitus. Exp Opin Invest Drugs 4: 525–536, 1995CrossRefGoogle Scholar
  45. 45.
    Rosen O: After insulin binds. Science 237: 1452–1458, 1987PubMedCrossRefGoogle Scholar
  46. 46.
    Olefsky JM: The insulin receptor: a multifunctional protein. Diabetes 3A: 1009–1116, 1990CrossRefGoogle Scholar
  47. 47.
    Myers MG, White MF: The new elements of insulin signaling insulin receptor substrate-1 and proteins with SH2 domains. Diabetes 42: 643–650, 1993.PubMedCrossRefGoogle Scholar
  48. 48.
    White MF, Kahn CR: The insulin signaling system. J Biol Chem 269: 14, 1994Google Scholar
  49. 49.
    Chou CK, Dull TJ, Russel DS, Ghezri R, Lebwohl D, Ullrich A, Rosen OM: Human insulin receptors mutated at the ATP-binding site lack protein tyrosine kinase activity and fail to mediate post-receptor effects of insulin. J Biol Chem 262: 1842–1847, 1987PubMedGoogle Scholar
  50. 50.
    McClain DA, Maegawa H, Lee J, Dull TJ, Ullrich A, Olefsky JM: A mutant insulin receptor with defective tyrosine kinase displays no biological activity and does not go endocytosis. J Biol Chem 262: 14663–14671, 1987PubMedGoogle Scholar
  51. 51.
    Swarup G, Cohen S, Garbers DL: Inhibition of membrane phosphotyrosyl protein phosphatase activity by vanadate. Biochem Biophys Res Commun 107: 1104–1109, 1982PubMedCrossRefGoogle Scholar
  52. 52.
    Tamura S, Brown TA, Dubler RE, Larner J: Insulin like effects of vanadate on glycogen synthase and on phosphorylation of 95,000 dalton subunit of the insulin receptor. Biochem Biophys Res Commun 113: 80–86, 1984CrossRefGoogle Scholar
  53. 53.
    Bernier M, Laird DM, Lane MD: Effect of vanadate on the cellular accumulation of ppl 5, an apparent product of insulin receptor tyrosine kinase action. J Biol Chem 263: 13626–13634, 1988PubMedGoogle Scholar
  54. 54.
    Gherzi R, Caratti C, Andraghetti G, Bertolini S, Montemurrd A, Sesti G, Cordera R: Direct modulation of insulin receptor protein tyrosine kinase by vanadate and anti-insulin receptor monoclonal antibodies. Biochem Biophys Res Commun 152: 1474–1480, 1988PubMedCrossRefGoogle Scholar
  55. 55.
    Pugazhenthi S, Khandelwal RL: Does the insulin-mimetic action of vanadate involve insulin receptor kinase? Mol Cell Biochem 217–218: 211–218, 1993CrossRefGoogle Scholar
  56. 56.
    Strout HV, Vicario PP, Saperstein R, Slater EE: The insulinmimetic effect of vanadate is not correlated with insulin receptor tyrosine kinase activity nor phosphorylation in mouse diaphragm in vivo. Endocrinology 124: 1918–1924, 1989PubMedCrossRefGoogle Scholar
  57. 57.
    Shisheva A, Shechter Y: Quercetin selectively inhibits insulin receptor function in vitro and the bioresponse of insulin and insulinomimetic agents in rat adipocytes. Biochemistry 31: 8059–8063, 1992PubMedCrossRefGoogle Scholar
  58. 58.
    Mooney RA, Bordwell KL, Luhowsky S, Casnelli JE: The insulinlike effect of vanadate on lipolysis in rat adipocytes is not accompanied by an insulin-like effect on tyrosine phosphorylation. Endocrinology 124: 422–429, 1989PubMedCrossRefGoogle Scholar
  59. 59.
    Blondel O, Simon J, Chevalier B, Portha B: Impaired insulin action but normal insulin receptor activity in diabetic rat liver: effect of vanadate. Am J Physiol 258: E459–E467, 1990PubMedGoogle Scholar
  60. 60.
    D’Onofrio F, Le MQ, Chiasson J-L, Srivastava AK: Vanadate dependent activation of mitogen activated protein (MAP) kinase in Chinese hamster ovary cells overexpressing a wild type human insulin receptor (CHO-HIRc). The Pharmacologist 35: 109, 1993Google Scholar
  61. 61.
    D’Onofrio F, Le MQ, Chiasson J-L, Srivastava AK: Activation of mitogen activated protein (MAP) kinases by vanadate is independent of insulin receptor autophosphorylation. FEBS Lett 340: 269–275, 1994PubMedCrossRefGoogle Scholar
  62. 62.
    Ray LB, Sturgill TW: Rapid stimulation by insulin of a serine/threonine kinase in 3T3-L1 adipocytes that phosphorylates microtubule associated protein-2 in vitro. Proc Natl Acad Sci USA 1502–1506, 1987Google Scholar
  63. 63.
    Sturgill, TW, Ray, LB, Erkson, E, Maller, JL.: Insulin-stimulated MAP-2 kinase phosphorylates and activates ribosomal s6 kinase II. Nature 334: 715–718, 1988PubMedCrossRefGoogle Scholar
  64. 64.
    Banerjee P, Ahmad MF, Grove JR, Kozlosky C, Price DJ, Avruch J: Molecular structure of a major insulin/mitogen-activated 70kDa s6 protein kinase. Proc Natl Acad Sci USA 87: 8550–8554, 1990PubMedCrossRefGoogle Scholar
  65. 65.
    Cobb MH: An insulin stimulated ribosomal protein kinase in 3T3-L1 cells. J Biol Chem 261: 12994–12999, 1986PubMedGoogle Scholar
  66. 66.
    Blenis J: Transduction via the MAP kinases: Proceed at your own RSK. Proc Natl Acad Sci (USA) 90: 5889–5892, 1993CrossRefGoogle Scholar
  67. 67.
    Pederson RA, Ramanadham S, Buchan A, McNeill JH: Long term effects of vanadyl treatment on streptozotocin-induced diabetes in rats. Diabetes 38: 1390–1395, 1989PubMedCrossRefGoogle Scholar
  68. 68.
    Kozma SC, Ferrari S, Bassand P, Siegmann M, Totty N, Thomas G: Cloning of the mitogen-activated s6 kinase from rat liver reveals an enzyme of the second messenger subfamily. Proc Natl Acad Sci USA 87: 7365–7369, 1990PubMedCrossRefGoogle Scholar
  69. 69.
    Chen R-H, Blenis J: Identification of Xenopus S6 protein kinase homologus (pp90rsk) in somatic cells: phosphorylation and activation during the initiation of cell proliferation. Mol Cell Biol 10: 3204–3215, 1. Ramasarma T, Crane FL: Does vanadium play a role in cellular regulation? Curr Topics Cell Regul 20: 247–301, 1991Google Scholar
  70. 70.
    Srivastava AK, Chiasson J-C, Chiasson J-L, Lacroix A, Windisch L: Biochemical characterstics of cytosolic and particulate forms of protein tyrosine kinases from N-methyl-N-nitrosourea (MNU)-induced rat mammmary carcinoma. Mol Cell Biochem 106: 87–97, 1991PubMedCrossRefGoogle Scholar
  71. 71.
    Cobb MH, Boulton TG, Robbins DJ: Extracellular signal-regulated kinases: ERKS in progress. Cell-Regul 2: 965–978, 1991PubMedGoogle Scholar
  72. 72.
    Chen R.-H, Chung J, Blenis J: Regulation of pp90rsk phosphorylation and s6 phosphotransferase activity in swiss 3T3 cells by growth factor — phorbol ester — and cyclic AMP-mediated signal transduction. Mol Cell Biol 11: 1861–1867, 1991PubMedGoogle Scholar
  73. 73.
    Nguyen TT, Scimeca J-C, Filloux C, Peraldi P, Carpentier J-L, Van Obberghen E: Co-regulation of the mitogen activated protein kinase, extracellular signal-regulated kinase 1 and the 90 kDa ribosomal s6 kinase in PC12 cells. Distinct effects of the neurotrophic factor, nerve growth factor and the mitogenic factor, Epidermal growth factor. J Biol Chem 268: 9803–9810, 1993PubMedGoogle Scholar
  74. 74.
    Tamemoto H, Kadowaki T, Tobe K, Yagi T, Sakura H, Hyakawa T, Terauchi Y, Ueki K, Kaurage Y, Satoh S, Sekihara H, Yoshioka S, Horikoshi H, Furuta Y, Ikawa Y, Kasuga M, Yazaki Y, Aizawa S: Insulin resistance and growth retardation in mice lacking insulin receptor substrate-1. Science 372: 182–186, 1994Google Scholar
  75. 75.
    Dent P, Lavoinne A, Nakielny S, Caudwell FB, Watt P, Cohen P: The molecular mechanism by which insulin stimulates glycogen synthesis in mammalian skeletal muscle. Nature 348: 302–308, 1990PubMedCrossRefGoogle Scholar
  76. 76.
    Cross DAE, Alessi DR, Vadenheede JR, McDowell HE, Hundal HS, Cohen P: The inhibition of glycogen synthase kinase-3 by insulin or insulin-like growth factor 1 in the rat skeletal muscle cell line L6 is blocked by worthmannin, but not by rapamycin: evidence that wortmannin blocks activation of the mitogen activated protein kinase pathway in L6 cells between ras and raf. Biochem J 303: 21–26, 1994PubMedGoogle Scholar
  77. 77.
    Welsh GI, Foulstone EJ, Young SW, Tavare JM, Proud CG: Wortmannin inhibits the effect of insulin and serum on the activities of glycogen synthase kinase-3 and mitogen activated protein kinase. Biochem J 303: 15–20, 1994PubMedGoogle Scholar
  78. 78.
    Shepherd PR, Nave BT, Siddle K: Insulin stimulation of glycogen synthesis and glycogen synthase activity is blocked by wortmannin and repamycin in 3T3-L1 adipcoytes: evidence for the involvement of phosphoinositde 3-kinase and p70 ribosomal protein S6 kinase. Biochem J 305: 25–28, 1995PubMedGoogle Scholar
  79. 79.
    Donella-Dean A, Lavoinne A, Marin O, Pinna LA, Cohen, P: An analysis of the substrate specificity of insulin-stimulated protein kinase-1. Biochem Biophys Acta 1178: 189–193, 1993CrossRefGoogle Scholar
  80. 80.
    Sutherland C, Cambell DG, Cohen P: Identification of insulin stimulated protein kinase-1 as the rabbit equivalent of rsk-2 identification of two threonine phophorylation during activation by mitogen activated protein kinase. Eur J Biochem 212: 581–588, 1993PubMedCrossRefGoogle Scholar
  81. 81.
    Sutherland C, Leighton IA, Cohen P: Identification of glycogen synthase kinase-3 by phosphorylation: new kinase connections in insulin and growth factor signalling. Biochem J 296: 15–19, 1993PubMedGoogle Scholar
  82. 82.
    Sutherland C, Cohen P: The alpha-isoform of glycogen synthase kinase-3 from rabbit skeletal muscle is inactivated by p70s6 kinase or MAP kinase-activated protein kinase-1 in vitro. FEBS Lett 338: 37–42, 1994PubMedCrossRefGoogle Scholar
  83. 83.
    Woodgett JR: A common denominator linking glycogen metabolism, nuclear oncogene and development. Trends Biochem Sci 16: 177–181, 1991PubMedCrossRefGoogle Scholar
  84. 84.
    Lin TA, Lawrence JC Jr: Activation of ribosomal protein s6 kinase does not increase glycogen synthesis or glucose transport in rat adipocytes. J Biol Chem 269: 21255–21261, 1994PubMedGoogle Scholar
  85. 85.
    Cheatham B, Vlahos CJ, Cheatham L, Wang L, Blenis J, Kahn CR: Phosphatidyl inositol 3-kinase activation is required for insulin stimulation of pp70s6k, DNA synthesis, and glucose transporter translocation. Mol Cell Biol 14: 4902–4911, 1994PubMedGoogle Scholar
  86. 86.
    Berger J, Hayes N, Szalkowski DM, Zhang B: PI3-kinase activation is required for insulin stimulation of glucose transport into L6 myotube. Biochem Biophys Res Commun 205: 570–576, 1994PubMedCrossRefGoogle Scholar
  87. 87.
    Finger DC, Hausdorff SF, Blenis J, Birnbaum MJ: Dissociation of pp70 ribosomal protein s6 kinase from insulin-stimulated glucose transport in 3T3-L1 adipocytes. J Biol Chem 268: 3005–3008, 1993Google Scholar
  88. 88.
    Goldfme AB, Folli F, Patti ME, Simonson DC, Kahn CR: Clinical trials of vanadium compounds in human diabetes mellitus. Can J Physiol Pharmacol 72 (suppl 3): 11, 1994Google Scholar
  89. 89.
    Fantus IG, Ahmad F, Deragon G: Vanadate augments insulin binding and prolongs insulin action in rat adipocytes. Endocrinology 127: 2716–2725, 1990PubMedCrossRefGoogle Scholar
  90. 90.
    Fantus IG, Ahmad F, Deragon G: Vanadate augments insulin stimulated tyrosine kinase activity and prolongs insulin action in rat adipocytes: evidence for transduction of amplitude of signaling into duration of response. Diabetes 43: 375–383, 1994PubMedCrossRefGoogle Scholar
  91. 91.
    Shisheva A, Shechter Y: Role of cytosolic tyrosine kinase in mediating insulin-like actions of vanadate in rat adipocytes. J Biol Chem 268: 6463–6469, 1993PubMedGoogle Scholar
  92. 92.
    Skolnik EY, Lee CH, Batzer A, Vincentine LM, Zhou M, Daly R, Myers MJ Jr, Backer JM, Ullrich A, White MF, Schlessinger J: The SH2/SH3 domain containing protein GRB2 interacts with tyrosinephosphorylated IRS-1 and she: implications for insulin control of ras signalling. The EMBO J 12: 1429–1436, 1993Google Scholar
  93. 93.
    Sarcevic B, Erikson E, Maller JL: Purification and characterization of a mitogen-activated protein kinase tyrosine phosphatase from Xenopus eggs. J Biol Chem 268: 25075–25083, 1993PubMedGoogle Scholar
  94. 94.
    Chung J, Grammer TC, Lemon KP, Kazlauskar A, Blenis J: PDGF-and insulin-independent pp70s6k activation mediated by phosphatidylinositol-3-OH kinase. Nature (London) 370: 71–75, 1994CrossRefGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1995

Authors and Affiliations

  • Sanjay K. Pandey
    • 1
    • 2
  • Jean-Louis Chiasson
    • 1
    • 2
  • Ashok K. Srivastava
    • 1
    • 2
  1. 1.Research Group On Diabetes and Metabolic RegulationCentre de Recherche/Hotel-Dieu de Montreal HospitalMontrealCanada
  2. 2.Department of MedicineUniversity of MontrealMontrealCanada

Personalised recommendations