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Protein Phosphorylations As a Mode of Insulin Action

  • Joseph Avruch
  • Raphael A. Nemenoff
  • Mark Pierce
  • Yan C. Kwok
  • Perry J. Blackshear

Abstract

Within minutes after the interaction of insulin with its receptor, marked changes occur in the metabolic pattern of the cell. In classic target tissues, insulin inhibits catabolic pathways (e.g., glycogenolysis and lipolysis), concurrently activating anabolic pathways (such as glycogen synthesis and de novo fatty acid synthesis). These effects are due to alterations in the activity of a variety of intracellular enzymes and transcellular transport processes. Over a longer period of time, insulin also participates in regulating the expression of specific genes and, in certain cell types, insulin modulates cell division and growth.

Keywords

Insulin Receptor Tyrosine Phosphorylation Protein Phosphorylation Rous Sarcoma Virus Insulin Receptor Tyrosine Kinase 
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.

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References

  1. 1.
    Robison, G.A., Butcher, R., and Sutherland, E.W., in 1971, cAMP, pp. 1–23, Academic Press, New York.Google Scholar
  2. 2.
    Lamer, J., and Villar-Palasi, C., 1971, Curr. Top. Cell. Regul. 3: 195–236.Google Scholar
  3. 3.
    Roach, P.J., Rosell, M., Rosell Perez, M., and Lamer, J., 1977, FEBS Lett. 80: 95–98.PubMedCrossRefGoogle Scholar
  4. 4.
    Sheorain, V.S., Khatra, B.S., and Soderling, T.R., 1982, J. Biol. Chem. 257: 3462–3470.PubMedGoogle Scholar
  5. 5.
    Uhing, R.J., Shikama, H., and Exton, J., 1981, FEBS Lett. 134: 185–188.PubMedCrossRefGoogle Scholar
  6. 6.
    Parker, P.J., Caudwell, F.B., and Cohen, P., 1983, Eur. J. Biochem. 130: 227–234.PubMedCrossRefGoogle Scholar
  7. 7.
    Lawrence, J.C., Hiken, J.F., DePaoli-Roach, A.A., and Roach, P.J., 1983, J. Biol. Chem. 258: 10710–10719.PubMedGoogle Scholar
  8. 8.
    Mukherjee, C., and Jungas, R.L., 1975, Biochem. J. 148: 229–235.PubMedGoogle Scholar
  9. 9.
    Denton, R.M., Hughes, W.A., Bridges, B.J., Brownsey, R.W., McCormack, S.G., and Stansbie, D., 1978, Horm. Cell Regul. 2: 191–208.Google Scholar
  10. 10.
    Engstrom, L., 1980, Mol. Aspects Cell Regul. 1: 11–30.Google Scholar
  11. 11.
    Claus, T.H., and Pilkis, S.J., 1981, Biochem. Actions Horm. 8: 209–271.Google Scholar
  12. 12.
    Fredrikson, G., Stralfors, P., Nilsson, N.O., and Belfrage, P., 1981, J. Biol. Chem. 256: 6311–6320.PubMedGoogle Scholar
  13. 13.
    Ingebritsen, T.S., Geelen, M.J.H., Evenson, K.J., and Gibson, D.M., 1979, J. Biol. Chem. 254: 9986–9989.PubMedGoogle Scholar
  14. 14.
    Vande Werve, G., Hue, L., and Hers, H.G., 1977, Biochem. J. 162: 135–142.PubMedGoogle Scholar
  15. 15.
    Marchmont, R.J., and Houslay, M.D., 1980, Nature, 286: 904–906.PubMedCrossRefGoogle Scholar
  16. 16.
    Krebs, E.G., 1972, Curr. Top. Cell. Regul. 5: 99–131.PubMedGoogle Scholar
  17. 17.
    Kono, T., and Barham, T.W., 1983, J. Biol. Chem. 248: 7417–7426.Google Scholar
  18. 18.
    Sneyd, J.G.T., Corbin, J.D., and Park, C.R., 1968, in Pharmacology of Hormonal Polypeptides and Proteins (H. Back, L. Martini, and R. Paoletti, eds.), p. 376, Plenum Press, New York.Google Scholar
  19. 19.
    Sica V., and Cuatrecasas, 1973, Biochemistry, 12: 2782–2291.CrossRefGoogle Scholar
  20. 20.
    Avruch, J., Leone, G., and Martin, D.B., 1974, J. Clin. Invest. 53: 3a.CrossRefGoogle Scholar
  21. 21.
    Avruch, J., Leone, G., and Martin, D.B., 1974, Diabetes 23: 348.Google Scholar
  22. 22.
    Avruch, J., Leone, G., and Martin, D.B., 1976, J. Biol. Chem. 251: 1505–1510.PubMedGoogle Scholar
  23. 23.
    Avruch, J., Leone, G., and Martin, D.B., 1976, J. Biol. Chem. 251: 1511–1515.PubMedGoogle Scholar
  24. 24.
    Crapo, L., Graham, W., and Avruch, J., 1980, Biochem. Biophys. Res. Commun. 94: 1331–1336.PubMedCrossRefGoogle Scholar
  25. 25.
    Blackshear, P.J., Nemenoff, R.A., and Avruch, J., 1982, Biochem. J. 204: 817–824.PubMedGoogle Scholar
  26. 26.
    Avruch, J., Witters, L.A., Alexander, M.C., and Bush, M.A., 1978, J. Biol. Chem. 253: 4754–5761.PubMedGoogle Scholar
  27. 27.
    Alexander, M.C., Kowaloff, E.M., Witters, L.A., Dennihy, D.T., and Avruch, J., 1979, J. Biol. Chem. 254: 8052–8056.PubMedGoogle Scholar
  28. 28.
    Blackshear, P.J., Nemenoff, R.A., and Avruch, J., 1983, Biochem. J. 214: 11–19.PubMedGoogle Scholar
  29. 29.
    Benjamin, W.B., and Singer, I., 1974, Biochim. Biophys. Acta 351: 28–42.PubMedGoogle Scholar
  30. 30.
    Benjamin, W.B., and Singer, I., 1975, Biochemistry 14: 3301–3309.PubMedCrossRefGoogle Scholar
  31. 31.
    Benjamin, W.B., and Clayton, N.L., 1978, J. Biol. Chem. 253: 1700–1707.PubMedGoogle Scholar
  32. 32.
    Ramakrishna, B., and Benjamin, W.B., 1979, J. Biol. Chem. 254: 9232–9236.PubMedGoogle Scholar
  33. 33.
    Fom, J., and Greengard, P., 1976, Arch, Biochem. Biophys. 176: 721–733.CrossRefGoogle Scholar
  34. 34.
    Hughes, W.A., Brownsey, R.W., and Denton, R.M., 1977, in Phosphorylated Proteins and Related Enzymes Pinna, LA (ed.), pp. 17–32, Information Retrieval, London.Google Scholar
  35. 35.
    Hughes, W.A., Brownsey, R.W., and Denton, R.M., 1980, Biochem. J. 192: 469–481.PubMedGoogle Scholar
  36. 36.
    Belsham, G.J., Brownsey, R.W., Hughes, W.A., and Denton, R.M., 1980, Diabetologia 18: 307–312.PubMedCrossRefGoogle Scholar
  37. 37.
    Belsham, G.J., Denton, R.M., and Tanner, M.J.A., 1980, Biochem. J. 192: 457–467.PubMedGoogle Scholar
  38. 38.
    Smith, C.J., Wejksnora, P.J., Warner, J.R., Rubin, C.S., and Rosen, O.M., 1979, Proc. Natl. Acad. Sci. USA 76: 2725–2729.PubMedCrossRefGoogle Scholar
  39. 39.
    Smith, C.J., Rubin, C.S., and Rosen, O.M., 1980, Proc. Natl. Acad. Sci. USA 77: 2641–2645.PubMedCrossRefGoogle Scholar
  40. 40.
    Haselbacher, G.K., Humbel, R.E., and Thomas, G., 1979, FEBS. Lett. 100: 185–187.PubMedCrossRefGoogle Scholar
  41. 41.
    Kasuga, M., Karlsson, F.A., and Kahn, R.C., 1982, Science 215: 185–187.PubMedCrossRefGoogle Scholar
  42. 42.
    Kasuga, M., Zick, Y., Blithe, D.L., Karlsson, F.A., Haring, H.U., and Kahn, C.R., 1982, J. Biol. Chem. 257: 9891–9894.PubMedGoogle Scholar
  43. 43.
    Cohen, S., Carpenter, G., and King, L., 1980, J. Biol. Chem. 255:4834–4842. ’Google Scholar
  44. 44.
    Nilsson, N.D., Stralfors, P., Fredrikson, G., and Belfrage, P., 1980, FEBS Lett. 111: 125–130.PubMedCrossRefGoogle Scholar
  45. 45.
    Nimmo, H.G., and Cohen, P., 1977, Adv. Cyclic Nucleotide Res. 8: 145–266.PubMedGoogle Scholar
  46. 46.
    Beavo, J.A., Bechtel, P.J., and Krebs, E.G., 1974, Proc. Natl. Acad. Sci. USA 71: 3580–3583.PubMedCrossRefGoogle Scholar
  47. 47.
    Soderling, T.R., Corbin, J.D., and Park, C.R., 1973, J. Biol. Chem. 248: 1822–1829.PubMedGoogle Scholar
  48. 48.
    Walkenbach, R.J., Hazen, R., and Lamer, J., 1978, Mol. Cell Biochem. 19: 31–41.PubMedCrossRefGoogle Scholar
  49. 49.
    Lamer, J., Galasko, G., Cheng, K., DePaoli-Roach, A.A., Huang, L., Duggy, P., and Kellog, I., 1979, Science, 206: 1408–1410.CrossRefGoogle Scholar
  50. 50.
    Ingebritsen, T.S., and Cohen, P., 1983, Science 221: 331–338.PubMedCrossRefGoogle Scholar
  51. 51.
    Huang, F.L., and Glinsman, W.H., 1976, Eur. J. Biochem. 70: 419–426.PubMedCrossRefGoogle Scholar
  52. 52.
    Foulkes, J.G., and Cohen, P., 1979, Eur. J. Biochem. 97: 251–256.PubMedCrossRefGoogle Scholar
  53. 53.
    Hemmings, B.A., Resink, T.J., and Cohen, P., 1982, FEBS. Lett. 150: 319–324.PubMedCrossRefGoogle Scholar
  54. 54.
    Khatra, B.S., Chiasson, J.L., Shikima, H.J., Exton, J.A., and Soderling, T.R., 1980, FEBS. Lett. 114: 253–256.PubMedCrossRefGoogle Scholar
  55. 55.
    Foulkes, J.G., Cohen, P., Strada, S.J., Everson, W.V., and Jefferson, L.S., 1982, J. Biol. Chem. 257: 12493–12496.PubMedGoogle Scholar
  56. 56.
    Nemenoff, R.A., Blackshear, P.B., and Avruch, J., 1983, J. Biol. Chem. 258: 9437–9443.PubMedGoogle Scholar
  57. 57.
    Manganiello, V., and Vaughn, M., 1973, J. Biol. Chem. 248: 7164–7170.PubMedGoogle Scholar
  58. 58.
    Makino, H., and Kono, T., 1980, J. Biol. Chem. 255: 7850–7854.PubMedGoogle Scholar
  59. 59.
    Loten, E.G., Assimacopoulos-Jeannet, F.D., Exton, J.A., and Park, C.R., 1978, J. Biol. Chem. 253: 746–757.PubMedGoogle Scholar
  60. 60.
    Heyworth, C.M., Wallace, A.V., and Houslay, M.D., 1983, Biochem. J. 214: 99–110.PubMedGoogle Scholar
  61. 61.
    Belsham, G.J., Brownsey, R.W., and Denton, R.M., 1982, Biochem. J. 204: 345–352.PubMedGoogle Scholar
  62. 62.
    Cottam, G.L., and Srere, P.A., 1969, Biochem. Biophys. Res. Commun. 35: 895–900.PubMedCrossRefGoogle Scholar
  63. 63.
    Alexander, M.C., Palmer, J.C., Pointer, R.H., Koumjian L., and Avruch, J., 1982, J. Biol. Chem. 257: 2049–2055.PubMedGoogle Scholar
  64. 64.
    Alexander, M.C., Palmer, J.C., Pointer, R.H., Koumjian, L., and Avruch, J., 1981, Biochim. Biophys. Acta 674: 37–47.PubMedCrossRefGoogle Scholar
  65. 65.
    Swergold, C.D., Rosen, O.M., and Rubin, C.S., 1982, J. Biol. Chem. 257: 4207–4215.PubMedGoogle Scholar
  66. 66.
    Pierce, M.W., Palmer, J.L., Keutmann, H.T., Hall, T.A., and Avruch, J., 1981, J. Biol. Chem. 256: 8867–8870.PubMedGoogle Scholar
  67. 67.
    Pierce, M.W., Palmer, J.L., Keutmann, H.T., Hall, T.A., and Avruch, J., 1982, J. Biol. Chem. 257: 10681–10686.PubMedGoogle Scholar
  68. 68.
    Avruch, J., Alexander, M.C., Palmer, J.L., Pointer, R.H., Nemenoff, R.A., and Pierce, M.W., 1981, Cold Spring Harbor Conf. Cell Prolif. 8: 759–770.Google Scholar
  69. 69.
    Ranganathan, N.S., Linn, T.C., and Srere, P.A., 1982, J. Biol. Chem. 257: 698–702.PubMedGoogle Scholar
  70. 70.
    Janski, A.M., Srere, P.A., Cornell, N.W., and Veech, R.L., 1979, J. Biol. Chem. 254: 9365–9368.PubMedGoogle Scholar
  71. 71.
    Witters, L.A., Moriarty, P., and Martin, D.B., 1979, J. Biol. Chem. 254: 6644–6649.PubMedGoogle Scholar
  72. 72.
    Brownsey, R.W., Hughes, W.A., and Denton, R.W., 1979, Biochem. J. 184: 23–32.PubMedGoogle Scholar
  73. 73.
    Brownsey, R.W., and Denton, R.M., 1982, Biochem. J. 202: 77–86.PubMedGoogle Scholar
  74. 74.
    Witters, L.A., 1981, Biochem. Biophys. Res. Commun. 100: 872–878.PubMedCrossRefGoogle Scholar
  75. 75.
    Witters, L.A., Kowaloff, E.M., and Avruch, J., 1979, J. Biol. Chem. 254: 245–248.PubMedGoogle Scholar
  76. 76.
    Witters, L.A., and Vogt, B., 1981, J. Lipid Res. 22: 364–369.PubMedGoogle Scholar
  77. 77.
    Witters, L.A., Tipper, J.P., and Bacon, G.W., 1983, J. Biol. Chem. 258: 5643–5648.PubMedGoogle Scholar
  78. 78.
    Brownsey, R.W., and Hardie, D.G., 1980, FEBS Leu. 120: 67–70.CrossRefGoogle Scholar
  79. 79.
    Hardie, D.G., and Grey, P.S., 1980, Eur. J. Biochem. 110: 167–177.PubMedCrossRefGoogle Scholar
  80. 80.
    Tipper, J., and Witters, L.A., 1982, Biochim. Biophys. Acta 715: 162–169.PubMedCrossRefGoogle Scholar
  81. 81.
    Tipper, J., Bacon, G.W., and Witters, L.A., 1983, Arch. Biochem. Biophys. 227: 386–396.PubMedCrossRefGoogle Scholar
  82. 82.
    Wool, I.G., 1979, Annu. Rev. Biochem. 48: 719–754.PubMedCrossRefGoogle Scholar
  83. 83.
    Wettenhall, R., Cohen, P., Caudwell, B., and Holland, R., 1982, FEBS Lett. 148: 207–213.PubMedCrossRefGoogle Scholar
  84. 84.
    Gressner, A., and Wool, LG., 1974, J. Biol. Chem. 249: 6917–6925.PubMedGoogle Scholar
  85. 85.
    Lastick, S.M., Neilson, O.J., and McConkey, E.H., 1977, Mol. Gen. Genet. 152: 223–230.PubMedCrossRefGoogle Scholar
  86. 86.
    Thomas, G., Siegmann, M., Kubler, A.M., Gordon, J., and Jimenez de Asua, L., 1980, Cell 19: 1015–1023.PubMedCrossRefGoogle Scholar
  87. 87.
    Thomas, G., Martin-Perez, J., Siegmann, M., and Otto, A., 1982, Cell 30: 235–242.PubMedCrossRefGoogle Scholar
  88. 88.
    Wettenhall, R.E.H., and Cohen, P., 1982, FEBS Leu. 140: 263–269.CrossRefGoogle Scholar
  89. 89.
    Lastick, S.M., and McConkey, E.H., 1981, J. Biol. Chem. 256: 583–585.PubMedGoogle Scholar
  90. 90.
    Martin-Perez, J., and Thomas, G., 1983, Proc. Natl. Acad. Sci. USA 80: 926–930.PubMedCrossRefGoogle Scholar
  91. 91.
    Martin-Perez, J., Siegmann, M., and Thomas, G., 1984, Cell 36: 287–294.PubMedCrossRefGoogle Scholar
  92. 92.
    Leader, D.P., 1980, in Molecular Aspects of Cell Regulation, (P. Cohen, ed.), Vol. 1, pp. 203–234, Elsevier—North-Holland, Amsterdam.Google Scholar
  93. 93.
    Belsham, G.J., and Denton, R.M., 1980, Biochem. Soc. Trans. 8: 832–833.Google Scholar
  94. 94.
    Garrison J.C., 1978, J. Biol. Chem. 253: 7091–7100.PubMedGoogle Scholar
  95. 95.
    Garrison, J.C., Borland, M.K., Florio, V.A., and Twible, D.N., 1979, J. Biol. Chem. 254: 7147–7156.PubMedGoogle Scholar
  96. 96.
    LeCam, A., 1982, J. Biol. Chem. 257: 8376–8385.Google Scholar
  97. 97.
    Vargas, A.M., Halestrap, A.P., and Denton, R.M., 1982, Biochem. J. 208: 221–229.PubMedGoogle Scholar
  98. 98.
    Steinberg, R.A., and Coffin, P., 1979, Cell 18: 719–726.PubMedCrossRefGoogle Scholar
  99. 99.
    Steinberg, R.A., 1981, Cold Spring Harbor Conf. Cell Prolif. 8: 179–193.Google Scholar
  100. 100.
    Garrison, J.C., Borland, M.K., Moyland, R.D., and Ballard, B.J., 1981, Cold Spring Harbor Conf. Cell Prolif. 8: 529–545.Google Scholar
  101. 101.
    Blackshear, P.J., Nemenoff, R.A., Bonventre, J.V., Cheung, J.Y., and Avruch, J., 1984, Amer. J. Physiol. (Cell Physiol.) 246: C439 - C449.Google Scholar
  102. 102.
    Rosen, O.M., Rubin, C.S., Cobb, M.H., and Smith, C.J., 1981, J. Biol. Chem. 256: 3630–3633.PubMedGoogle Scholar
  103. 103.
    Cobb, M.H., and Rosen, O.M., 1983, J. Biol. Chem. 258: 12472–12481.PubMedGoogle Scholar
  104. 104.
    Perisic, O., and Traugh, J.A., 1983, J. Biol. Chem. 258: 9589–9592.PubMedGoogle Scholar
  105. 105.
    Brownsey, R.W., Edgell, N.J., Hopkirk, T.J., Denton, R.M., 1984, Biochem. J. 218: 733–743.PubMedGoogle Scholar
  106. 106.
    Ramakrishna, S., and Benjamin, W.B., 1981, FEBS Lett. 124: 140–144.PubMedCrossRefGoogle Scholar
  107. 107.
    Ramakrishna, S., Pucci, D.L., and Benjamin, W.B., 1981, J. Biol. Chem. 256: 10213–10216.PubMedGoogle Scholar
  108. 108.
    Van Obberghen, E., and Kowalski, 1982, FEBS Lett. 143: 179–182.PubMedCrossRefGoogle Scholar
  109. 109.
    Kasuga, M., Zick, Y., Blithe, D.L., Crettaz, M., and Kahn, C.R., 1982, Nature 298: 667–669.PubMedCrossRefGoogle Scholar
  110. 110.
    Petruzelli, L.M., Ganguly, S., Smith, C.J., Cobb, M.H., Rubin, C.S., and Rosen, O.M., 1982, Proc. Natl. Acad. Sci. USA 79: 6790–6796.CrossRefGoogle Scholar
  111. 111.
    Avruch, J., Nemenoff, R.A., Blackshear, P.J., Pierce, M.W., and Osathanondh, R., 1982, J. Biol. Chem. 257: 15162–15166.PubMedGoogle Scholar
  112. 112.
    Nemenoff R.A., Kwok, Y.C., Shulman, G.I., Blackshear, P.J., Osathanondh, R., and Avruch, J., 1984, J. Biol. Chem. 259: 5058–5065.PubMedGoogle Scholar
  113. 112a.
    Rosen, O.M., Herrera, R., Olowe, Y., Petruzelli, L.M., and Cobb, M.H., 1983, Proc. Natl. Acad. Sci. U.S.A. 80: 3237–3240.PubMedCrossRefGoogle Scholar
  114. 112b.
    Kono, T., Robinson, F.W., Sarver, J.A., Vega, F.V., and Pointer, R.H., 1977, J. Biol. Chem. 252: 2226–2233.PubMedGoogle Scholar
  115. 112c.
    Siegel, J., and Olefsky, J.M., 1980, Biochemistry 19: 2183–3190.PubMedCrossRefGoogle Scholar
  116. 112d.
    Häring, H.U., Bierman, E., and Kemmler, W., 1981, Amer. J. Physiol. 240: E556 - E565.PubMedGoogle Scholar
  117. 113.
    Roth, D.A., and Carrell, D.J., 1983, Science 219: 299–301.PubMedCrossRefGoogle Scholar
  118. 114.
    Van Obberghen, E., Rossi, B., Kowalski, A., Gazzaro, H., and Ponziog, G., 1983, Proc. Natl. Acad. Sci. USA 809: 945–949.CrossRefGoogle Scholar
  119. 115.
    Shia, M., and Pilch, C., 1983, Biochemistry 22: 717–721.PubMedCrossRefGoogle Scholar
  120. 116.
    Sugden, P.H., Holladay, L.A., Reimann, E.M., and Corbin, J.B., 1976, Biochem. J. 159: 409–422.PubMedGoogle Scholar
  121. 117.
    Haring, H.U., Kasuga, M., and Kahn, C.R., 1983, Biochem. Biophys. Res. Commun. 108: 1538–1545.CrossRefGoogle Scholar
  122. 118.
    Hunter, T., and Sefton, B.M., 1982, in Molecular Aspects of Cellular Regulation (Cohen, P., and Van Heyningen, S., eds.), Vol. 2, pp. 337–370, Elsevier-North-Holland, Amsterdam.Google Scholar
  123. 119.
    Hunter, T., and Cooper, J.A., 1981, Cell 24: 741–752.PubMedCrossRefGoogle Scholar
  124. 120.
    Cooper, J.A., Bowen-Pope, D.G., Raines, E., Ross, R., and Hunter, T., 1982, Cell 31: 263–273.PubMedCrossRefGoogle Scholar
  125. 121.
    Sefton, B.M., Hunter, T., Boll, E.H., and Singer, S.J., 1981, Cell 24: 165–174.PubMedCrossRefGoogle Scholar
  126. 122.
    Cooper, J.A., Reiss, N.A., Schwartz, R.J., and Hunter, T., 1983, Nature 302: 218–223.PubMedCrossRefGoogle Scholar
  127. 123.
    Frackelton, A.R., Ross, A.H., and Eisen, H.N., 1983, Mol. Cell Biol. 3: 1341–1352.Google Scholar
  128. 124.
    Ross, A.H., Baltimore, D., and Eisen, H.N., 1981, Nature 294: 654–656.PubMedCrossRefGoogle Scholar
  129. 125.
    Wong, T.W., and Goldberg, A.R., 1981, Proc. Natl. Acad. Sci. USA 78: 7412–7416.PubMedCrossRefGoogle Scholar
  130. 126.
    Decker, S., 1981, Proc. Natl. Acad. Sci. USA 78: 4112–4115.PubMedCrossRefGoogle Scholar
  131. 127.
    Spivak, J.G., Erikson, R.L., and Maller, J.L., 1984, Molecular and Cell Biol.,in press.Google Scholar

Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • Joseph Avruch
    • 1
    • 2
    • 3
  • Raphael A. Nemenoff
    • 1
    • 2
    • 3
  • Mark Pierce
    • 1
    • 2
    • 3
  • Yan C. Kwok
    • 1
    • 2
    • 3
  • Perry J. Blackshear
    • 1
    • 2
    • 3
  1. 1.Howard Hughes Medical Institute LaboratoryHarvard Medical SchoolBostonUSA
  2. 2.Diabetes Unit and Medical ServicesMassachusetts General HospitalBostonUSA
  3. 3.Department of MedicineHarvard Medical SchoolBostonUSA

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