Skip to main content
SpringerLink
Log in
Book cover

Growth Hormone pp 17–35Cite as

Signal Transduction Through the Growth Hormone Receptor

  • Chapter

Part of the book series: Endocrine Updates ((ENDO,volume 4))

Abstract

The importance of the cloned growth hormone (GH) receptor in the regulation of postnatal somatic growth is evidenced by the demonstration of point mutations and deletions in the gene encoding the GH receptor in Laron type dwarfism (1,2) and sex linked dwarfism in the chicken (3,4). Further, GH receptor gene deletion in mice results in a growth retarded phenotype (5). The mechanism by which the GH receptor mediates the general pleiotropic and specific somatic responses to its ligand have only recently begun to be understood. This review provides a brief discourse on the signal transduction pathways which have been demonstrated to be utilized by GH. The identification of such pathways, at least, provides a basis for understanding the pleiotropic actions of GH.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Godowski PJ, Leung DW, Meachem LR, Galgani JP, Helmiss R, Keret R, Rotwein P, Parks JS, Laron Z, Wood WI (1989) Characterization of the human growth hormone receptor gene and demonstration of a partial gene deletion in two patients with Laron type dwarfism. Proc. Natl. Acad. Sci. USA 86: 8083–8087

    Article  PubMed  CAS  Google Scholar 

  2. Amselem S, Duquesnoy P, Attree O, Novelli G, Bousnina S, Postel-Vinay MC, Goosens M (1989) Laron dwarfism and mutations of the growth hormone receptor gene. N. Engl. J. Med. 321: 989–995

    Article  PubMed  CAS  Google Scholar 

  3. Duriez B, Sobrier ML, Duquesnoy P, Tixier-Boichard M, Decuypere E, Coquerelle C, Zeman M, Goosens M, Amselem S (1993) A naturally occurring growth hormone receptor mutation: in vivo and in vitro evidence for the functional importance of the WS motif common to all members of the cytokine receptor superfamily. Mol. Endocrinol. 7: 806–814

    Article  PubMed  CAS  Google Scholar 

  4. Huang N, Cogburn LA, Agarwal SK, Marks HL, Burnside J (1993) Overexpression of a truncated growth hormone receptor in the sex linked dwarf chicken. Mol. Endocrinol 7: 1391–1398

    Article  PubMed  CAS  Google Scholar 

  5. Zhou Y, Xu BC, Maheshwari H, He L, Reed M, Lozykowski M, Chen N, Knapp JR, Cataldo LA, Okada S, Wagner TE, Baumann G, Kopchick JJ (1997) A mouse model for Laron syndrome produced by targeted disruption of the growth hormone receptor/binding protein gene. Proc 79th Ann. Meeting Endo. Soc. (Abstract p341)

    Google Scholar 

  6. Cosman D., Lyman SD., Idzerda RL., Beckmann MR, Park LS., Goodwin RG., March CJ (1990) A new cytokine receptor superfamily. TIBS 15: 265–270

    PubMed  CAS  Google Scholar 

  7. Kitamura T, Ogorochi T, Miyajima A (1994) Multimeric cytokine receptors. TEM. 5: 8–13

    PubMed  CAS  Google Scholar 

  8. Ihle JN, Witthuhn BA, Quelle FW, Yamamoto K, Silvennoinen O (1995) Signalling through the haemopoietic cytokine receptors. Ann. Rev. Immunol. 13:369–398

    Article  CAS  Google Scholar 

  9. Bazan Jf (1989) A novel family of growth factor receptors. Biochem. biophys. Res. commun. 164: 788–795

    Article  PubMed  CAS  Google Scholar 

  10. Patthy L (1990) Homology of a domain of the growth hormone/prolactin receptor family with type III modules of fibronectin. Cell 61: 13–14

    Article  PubMed  CAS  Google Scholar 

  11. Waters MJ (1997) “The Growth Hormone Receptor” Handbook of Physiology

    Google Scholar 

  12. vol5 ch14; editor JL Kostyo; Oxford University Press.

    Google Scholar 

  13. Frank SJ, Yi W, Zhao Y, Goldsmith JF, Gilliland G, Jiang J, Sakai I, Kraft AS (1995) Regions of the JAK2 tyrosine kinase required for coupling to the growth hormone receptor. J. Biol. Chem. 270: 14776–14785

    Article  PubMed  CAS  Google Scholar 

  14. Goujon L, Allevato G, Simonin G, Paquereau L, Le Cam A, Clark J, Nielsen JH, Djiane J, Postel-Vinay M-C, Edery M, Kelly PA (1994) Cytoplasmic sequences of the growth hormone receptor necessary for signal transduction. Proc. Natl. Acad. USA 91: 957–961

    Article  CAS  Google Scholar 

  15. VanderKuur J, Wang X, Zhang L-Y, Campbell G, Billestrup N, Norstedt G, Carter-Su C (1994) Critical cytoplasmic domains of the growth hormone receptor for JAK2 activation, MAP kinase activation and tyrosine phosphorylation of cellular proteins. J. Biol. Chem. 269: 21709–21717

    PubMed  CAS  Google Scholar 

  16. Wang YD, Wong K, Wood WI (1995) Intracellular tyrosine residues of the human growth hormone receptor are not required for the signalling of proliferation or JAK-STAT activation. J. Biol. Chem 270: 7021–7024

    Article  PubMed  CAS  Google Scholar 

  17. Tanner JW, Chen W, Young RL, Longmore GD, Shaw AS (1995) The conserved box 1 motif of cytokine receptors is required for association with JAK kinases. I biol. Chem. 270:6523–6530

    CAS  Google Scholar 

  18. Wells JA, Cunningham BC, Fuh G, Lowman HB, Bass SH, Mulkerrin MG, Ultsch M, Devos AM (1993) The molecular basis for growth hormone — receptor interactions. Rec. Prog. Horm. Res. 48: 253–275

    PubMed  CAS  Google Scholar 

  19. De Vos A. M., Ultsch M. and Kossiakoff A. A. (1992) Human growth hormone and extracellular domain of its receptor: Crystal structure of the complex. Science 255:306–312.

    Article  PubMed  Google Scholar 

  20. Cunningham BC, Ultsch M, DeVos AM, Mulkerrin MG, Clauser KR, Wells JA (1991) Dimerization of the extracellular domain of the hGH receptor by a single hormone molecule. Science 254: 821–825

    Article  PubMed  CAS  Google Scholar 

  21. Fuh G, Cunningham BC, Fukunaga R, Nagata S, Goeddel DV, Wells JA 1992 Rational design of potent antagonists to the human growth hormone receptor. Science 256: 1677–1680

    Article  PubMed  CAS  Google Scholar 

  22. Cunningham BC, Wells JA (1993) Comparison of a structural and functional epitope. J. Mol. Biol. 234: 554–563

    Article  PubMed  CAS  Google Scholar 

  23. Chen WY, Wight DC, Wagner TE, Kopcnick JJ (1990) Expression of a mutated bovine GH gene suppresses growth of transgenic mice. Proc. Natl. Acad. Sci. USA87: 5061–5065

    Article  Google Scholar 

  24. Ross RJ, Esposito N, Shen XY, Von Laue S, Chew SL, Dobson PR, Postel-Vinay MC, Finidori J (1997) A short isoform of the human growth hormone receptor functions as a dominant negative inhibitor of the full length receptor and generates large amounts of binding protein. Mol. Endocrinol. 11:265–273

    Article  PubMed  CAS  Google Scholar 

  25. Waters MJ, Rowlinson SW, Clarkson RW et al., Signal transduction by the growth hormone receptor. Proc. Soc. Exp. Biol. Med. 206: 216–220

    Google Scholar 

  26. Kishimoto T, Taga T, Akira S (1994) Cytokine signal transduction. Cell 76: 253–262

    Article  PubMed  CAS  Google Scholar 

  27. Livnah O, Stura EA, Johnson DL, Middleton SA, Mulcahy LS, Wrighton NC, Dower WJ, Jolliffe LK, Wilson IA (1996) Functional mimicry of a protein hormone by a peptide agonist. Science 273: 464–471

    Article  PubMed  CAS  Google Scholar 

  28. Argetsinger LS, Campbell GS, Yang X, Witthun BA, Silvennoinen O, Ihle JN, Carter-Su C. (1993) Identification of JAK2 as a growth hormone receptor associated kinase. Cell 74:1–20

    Article  Google Scholar 

  29. Foster C. M., Shafer J. A., Rozsa F. W., Wang X., Lewis S. D., Renken D.A., Natale J.E., Schwartz J. and Carter-Su C. (1988) Growth hormone promoted tyrosyl phosphorylation of growth hormone receptors in murine 3T3-F442A fibroblasts and adipocytes. Biochemistry 27:326–334.

    Article  PubMed  CAS  Google Scholar 

  30. Silva CM, Day RN, Weber MJ, Thoraer MO (1993) Human growth hormone receptor is characterized as the 134 kDa tyrosine phosphorylated protein activated by GH treatment in IM-9 cells. Endocrinology 133: 2307–2312

    Article  PubMed  CAS  Google Scholar 

  31. Carter-Su C, King AP, Argetsinger LS, Smit LS, Vanderkuur J, Campbell GS (1996) Signalling pathway of GH. Endocrin. J. 43Suppl:S65–70

    Article  CAS  Google Scholar 

  32. Smit LS, Meyer DJ, Billestrup N, Norstedt G, Schwartz J, Carter-Su C (1996) The role of the growth hormone receptor and JAK1 and JAK2 kinases in the activation of STATsl,3 and 5 by growth hormone. Mol. Endocrinol. 10: 519–533

    Article  PubMed  CAS  Google Scholar 

  33. Johnston JA, Kawamura AM, Kirken RA, Chen YQ, Blake TB, Shibuya K, Ortaldo JR, McVicar DW, O’Shea JJ (1994) Phosphorylation and activation of Janus kinase 3 in response to interleukin 2. Nature 370: 151–153

    Article  PubMed  CAS  Google Scholar 

  34. Klingmuller U, Lorenz U, Cantley LC, Neel BG, Lodish HF (1995) Specific recruitment of SH-PTP1 to the erythropoietin receptor causes inactivation of JAK2 and termination of the proliferative signals. Cell 80: 729–738

    Article  PubMed  CAS  Google Scholar 

  35. Kim SO, Jiang J, Yi WS, Feng GS, Frank SJ (1997) Interaction of the SH2 containing protein tyrosine Phosphatase SHP-1 and SHP-2 with the GH receptor-JAK2 complex. Proc. 79th Ann. Meet. Endocrine Society (Abstract 205)

    Google Scholar 

  36. Hackett RH, Wang YD, Sweitzer S, Feldman G, Wood WI, Lamer AC (1997) Mapping of a cytoplasmic domain of the human growth hormone receptor that regulates rates of inactivation of JAK2 and STAT proteins. J. Biol. Chem. 272: 11128–11132

    Article  PubMed  CAS  Google Scholar 

  37. Yin T, Shen R, Feng GS, Yang YC (1997) Molecular characterization of specific interactions between SHP-2 Phosphatase and JAK tyrosine kinases. J. Biol. Chem. 272: 1032–1037

    Article  PubMed  CAS  Google Scholar 

  38. Vanderkuur JA, Allevato G, Billestrup N, Norstedt G, Carter-Su C (1995) Growth hormone promoted tyrosyl phosphorylation of shc proteins and shc association with Grb2. J. Biol. Chem. 270: 7587–7593

    Article  PubMed  CAS  Google Scholar 

  39. He TC, Jiang N, Zhuang H, Wojchowski DM (1995) Eryhtropoietin induced recruitment of shc via a receptor phosphotyrsoine independent JAK2 associated pathway. J. Biol. Chem. 270: 11055–11061

    Article  PubMed  CAS  Google Scholar 

  40. Giordano V, DeFalco G, Chiari R, Quinto I, Pelicci PG, Bartholomew L, Delmastro P, Gadina M (1997) Shc mediates IL-6 signalling by interacting with gpl30 and JAK2 kinase. J. Immunol. 158: 4097–4103

    PubMed  CAS  Google Scholar 

  41. Takahashi-Tezuka M, Hibi M, Fujitani Y, Fukuda T, Yamaguchi T, Hirano T (1997) Tec tyrosine kinase links the cytokine receptors to PI-3 kinase probably through JAK. Oncogene 14: 2273–2282

    Article  PubMed  CAS  Google Scholar 

  42. Uddin S, Sher DA, Alsayed Y, Pons S, Colamonici OR, Fish EN, White MF, Platanias LC (1997) Interaction of p59 fyn with interferon activated JAK kinases. Biochem. Biophys. Res. Commun. 235: 83–88

    Article  PubMed  CAS  Google Scholar 

  43. Sotiropoulos A, Moutoussamy S, Renaudie F, Clauss M, Kayser C, Gouilleux F, Kelly PA, Finidori J (1996) Differential activation of STAT3 and STAT5 by distinct regions of the growth hormone receptor. Mol. Endocrinol. 10: 998–1009

    Article  PubMed  CAS  Google Scholar 

  44. Yi W, Kim SO, Jiang J, Park SH, Kraft AS, Waxman DJ, Frank SJ (1996) Growth hormone receptor cytoplasmic domain differentially promotes tyrosine phosphorylation of signal transducers and activators of transcription 5b and 3 by activated JAK2 kinase. Mol. Endocrinol. 10: 1425–1443

    Article  PubMed  CAS  Google Scholar 

  45. Wood TJJ, Sliva D, Lobie PE, Gouilleux F, Mui AL, Groner B, Norstedt G, Haldosen LA (1997) Specificity of transcriptiona enhancement via the STAT responsive element in the serine protease inhibitor 2.1 promoter. Mol. Cell. Endocrinol. 130:69–81

    Article  PubMed  CAS  Google Scholar 

  46. Moldrup A, Nielsen JH, Billestrup N (1995) Association of p59 fyn with the intracellular domain of the GH receptor. 77th Endocrine Soc. Meet. (Abstract)

    Google Scholar 

  47. Yu CL, Burakoff SJ (1997) Involvement of proteasomes in regulating JAK-STAT pathways upon interleukin-2 stimulation. J. Biol. Chem. 272: 14017–14020

    Article  PubMed  CAS  Google Scholar 

  48. Endo TA, Masuhara M, Yokouchi M, Suzuki R, Sakamoto H, Mitsui K, Matsumoto A, Tanimura S, Ohtsubo M, Misawa H, Miyazaki T, Leonor N, Taniguchi T, Fujita T, Kanakura Y, Komiya S, Yoshimura A (1997) A new protein containing an SH2 domain that inhibits JAK kinases. Nature 387: 921–924

    Article  PubMed  CAS  Google Scholar 

  49. Wiedermann CJ, Reinisch N, Braunsteiner H 1993 Stimulation of monocyte Chemotaxis by human growth hormone and its deactivation by somatostatin. Blood 82: 954–960

    PubMed  CAS  Google Scholar 

  50. Goh ELK, Pircher TJ, Wood TJJ, Norstedt G, Graichen R, Lobie PE (1997) Growth hormone induced reorganization of the actin cytoskeleton is not required for STAT5 mediated transcription. Endocrinology 138: 3207–3215

    Article  PubMed  CAS  Google Scholar 

  51. Guan JL, Chen HC (1996) Signal transduction in cell matrix interactions. Int. Rev.Cytol. 168:81–121

    Article  PubMed  CAS  Google Scholar 

  52. Ilic D, Damsky CH, Yamamoto T (1997) Focal adhesion kinase: at the crossroads of signal transduction. J. Cell. Sci. 110: 401–407

    PubMed  CAS  Google Scholar 

  53. Chen HC, Guan JL (1994) Stimulation of phosphatidylinositol 3 kinase association with focal adhesion adhesion kinase by platelet derived growth factor. J. Biol. Chem. 269: 31229–31233

    PubMed  CAS  Google Scholar 

  54. Schlaepfer DD, Hunter T (1997) Focal adhesion kinase overexpression enhances ras dependent integrin signalling to ERK2/mitogen activated protein kinase through interactions with and activation of c-src. J. Biol. Chem. 272:13189–13195

    Article  PubMed  CAS  Google Scholar 

  55. Ridderstrale M, Tornqvist H (1994) PI-3 kinase inhibitor wortmannin blocks the insulin like effects of growth hormone in isolated rat adipocytes. Biochem. Biophys. Res. Commun. 203: 306–310

    Article  PubMed  CAS  Google Scholar 

  56. Winston LA, Hunter T (1995) JAK2, Ras, Raf are reuired for activation of ERK/ mitogen activated protein kinase by growth homrone. J. Biol. Chem. 270: 30837–30840

    Article  PubMed  CAS  Google Scholar 

  57. Hanks SK, Polte TR (1997) Signalling through focal adhesion kinase. Bioessays 19: 137–145

    Article  PubMed  CAS  Google Scholar 

  58. Treisman R (1996) Regulation of transcription by MAP kinase cascades. Curr. Opin. Cell. Biol. 8: 205–215

    Article  PubMed  CAS  Google Scholar 

  59. Campbell GS, Pang L, Miyasaka T, Saltiel AR, Carter-Su C (1992) Stimulation by growth hormone of MAP kinase activity in 3T3-F442A fibroblasts. J. Biol. Chem. 267: 6074–6080

    PubMed  CAS  Google Scholar 

  60. Möller C, Hansson A, Enberg B, Lobie PE, Norstedt G (1992) Growth hormone induction of tyrosine phosphorylation and activation of mitogen activated protein kinases in cells transfected with rat GH receptor cDNA. J. Biol. Chem. 267: 23403–23408

    PubMed  Google Scholar 

  61. Winston LA, Bertics PJ (1992) Growth hormone stimulates the tyrosine phosphorylation of 42-kDa and 45 K-Da ERK related proteins. J. Biol. Chem. 267:4747–4751

    PubMed  CAS  Google Scholar 

  62. Tanaka S, Ouchi T, Hanafusa H (1997) Downstream of crk adaptor signalling pathway: activation of jun kinase by v-crk through the guanine nucleotide exchange protein C3G. Proc. Natl. Acad. Sci. USA. 94: 2356–2361

    Article  PubMed  CAS  Google Scholar 

  63. Han Y, Leaman DW, Watling D, Rogers NC, Groner B, Kerr IM, Wood WI, Stark GR (1996) Participation of JAK and STAT proteins in growth hormone induced signalling. J. Biol. Chem. 271: 5947–5952

    Article  PubMed  CAS  Google Scholar 

  64. Vanderkuur JA, Butch ER, Waters SB, Pessin JE, Guan KL, Carter-Su C (1997) Signalling molecules involved in cuopling growth hormone receptor to mitogen activated protain kinase activation. Endocrinology 138: 4301–4307

    Article  PubMed  CAS  Google Scholar 

  65. Kilgour E, Gout I, Anderson NG (1996) Requirement for phosphoinositide 3-OH kinase in growth hormone signalling to the mitogen activated protein kinase and p70 s6k pathways. Biochem. J. 315:517–522

    PubMed  CAS  Google Scholar 

  66. Davis RJ (1993) The mitogen activated protein kinase signal transduction pathway. J. Biol. Chem. 268: 14553–14556

    PubMed  CAS  Google Scholar 

  67. Pircher TJ, Flores-Morales A, Mui AL, Saltiel AR, Norstedt G, Gustafsson JA, Haldosen LA (1997) Mitogen activated protein kinase kinase inhibition decreases growth hormone stimulated transcription mediated by STAT5. Mol. Cell. Endocrinol., in press.

    Google Scholar 

  68. Anderson NG (1993) Similtaneous activation of p90rsk and p70s6k by growth hormone in 3T3-F442A pre-aadipocytes. Biochem. Biophys. Res. Commun. 193: 284–290

    Article  PubMed  CAS  Google Scholar 

  69. Tollet P, Hamberg M, Gustafsson JA, Mode A (1995) Growth hormone signalling leading to CYP2C12 gene expression in rat hepatocytes involves phospholipase A2. J. Biol. Chem. 270: 12569–12577

    Article  PubMed  CAS  Google Scholar 

  70. Gurland G, Ashcom G, Cochran BH, Schwartz J (1990) Rapid events in growth hormone action. Induction of c-fos and c-jun transcription in 3T3-F442A preadipocytes. Endocrinology 127: 3187–3195

    CAS  Google Scholar 

  71. Hodge CL, Liao JF, Ho PF, Schwartz J (1997) GH stimulated phosphorylation of ELK-1 or related protein contributes to c-fos transcription through the SRE. Proc. 79th Meet. Endo. Soc. (Abstract p73)

    Google Scholar 

  72. Meyer DJ, Campbell GS, Cochran BH, Argetsinger LS, Larner AC, Finbloom DS, Carter-Su C 1994 Growth hormone induces a DNA binding factor related to Interferon stimulated 91 KDa transcription factor. J. Biol. Chem. 269: 4701–4704

    PubMed  CAS  Google Scholar 

  73. Campbell GS, Meyer DJ, Raz R, Levy DE, Schwartz J, Carter-Su C (1995) Activation of acute phase response factor (APRF) / STAT3 transcription factor by growth hormone. J. Biol. Chem. 270: 3974–3979

    Article  PubMed  CAS  Google Scholar 

  74. Sotiropoulos A, Moutoussamy S, Binart N, Kelly PA (1995) The membrane proximal region of the cytoplasmic domain of the growth hormone receptor is involved in the activation of STAT3. FEBS Letters 369: 169–172

    Article  PubMed  CAS  Google Scholar 

  75. Wood TJJ, Sliva D, Lobie PE, Pircher TJ, Gouilleux F, Wakao H, Gustafsson J-Â, Groner B, Norstedt G, Haidosen L-A 1995 Mediation of growth hormone-dependent transcriptional activation by mammary gland factor/stat5. J Biol Chem 270:9448–9453

    Article  PubMed  CAS  Google Scholar 

  76. Waxman DJ, Ram PA, Park SH, Choi HK (1995) Intermittent plasma growth hormone triggers tyrosine phosphorylation and nuclear translocation of a liver expressed, Stat5 related DNA binding protein. Proposed role as a regulator of male specific gene transcription. J. Biol. Chem. 270: 13262–13270

    Article  PubMed  CAS  Google Scholar 

  77. Bergard PL, Shih HM, Towle HC, Schwarzenberg SJ, Berry SA 1995 Growth hormone induction of hepatic serine protease inhibitor 2.1 transcription is mediated by a STAT5 related factor binding synergistically to two gamma activated sites. J. Biol. Chem. 270: 24903–24910

    Article  Google Scholar 

  78. Rivera RM, Miranti CK, Misra RP, Ginty DD, Chen RH, Blenis J, Greenberg ME (1993) A growth factor induced kinase phosphorylates the serum response factor at a site that regulates its DNA binding activity. Mol. Cell. Biol. 13: 6260–6273

    PubMed  CAS  Google Scholar 

  79. Meyer DJ, Stephenson EW, Johnson L, Cochran BH, Schwartz J (1993) The serum response element can mediate the induction of c-fos by growth hormone. Proc. Natl. Acad. Sci. USA 90: 6721–6725

    Article  PubMed  CAS  Google Scholar 

  80. Horvath CM, Darnell JE (1997) The state of the STATs. Curr. Opin. Cell. biol. 9: 233–239

    Article  PubMed  CAS  Google Scholar 

  81. Okazaki K, Sagata N (1995) The mos/map kinase pathway stabilizes c-fos by phosphorylation and augments its transforming activity in NIH 3T# cells. EMBO. J. 14: 5048–5059

    PubMed  CAS  Google Scholar 

  82. Davidson MB (1987) Effect of growth hormone on carbohydrate and lipid metabolism. Endocrine Rev. 8: 115–131

    Article  CAS  Google Scholar 

  83. Eisenhauser KM, Chun SY, Billig H, Hseuh AJ (1995) Growth hormone suppression of apoptosis in preovulatory rat follicles and partial neutralization by insulin like growth factor binding protein. Biol. Reprod. 53: 13–20

    Article  Google Scholar 

  84. Argetsinger LS, Hsu GW, Myers MG, Billestrup N, White MF, Carter-Su C (1995) Growth hormone, interferon gamma and leukaemia inhibitory factor promoted tyrosyl phosphorylation of insulin receptor substrate-1. J. Biol. Chem. 270: 14685–14692

    Article  PubMed  CAS  Google Scholar 

  85. Argetsinger LS, Norstedt G, Billestrup N, White MF, Carter-Su C (1996) Growth hormone, interferon gamma and leukaemia inhibitory factor utilize insulin receptor substrate 2 in intracellular signalling. J. Biol. Chem. 271: 29415–29421

    Article  PubMed  CAS  Google Scholar 

  86. Ridderstrale M, Degerman E, Tornqvist H (1995) Growth hormone stimulates the tyrosine phosphorylation of the insulin receptor substrate-1 and its association with phosphatidylinositol 3-kinase in primary adipocytes. J. Biol. Chem. 279: 3471–3474

    Google Scholar 

  87. Souza SC, Frick GP, Yip R, Lobo RB, Tai LR, Goodman HM (1994) Growth hormone activation of insulin receptor substrate-1. J. Biol. Chem. 269: 30085–30088

    PubMed  CAS  Google Scholar 

  88. Lavan BE, Fantin VR, Chang ET, Lane WS, Keller SR, Lienhard GE (1997) A novel 160 kDa phosphotyrosine protein in insulin treated embryonic kidney cells is a new member of the insulin receptor substrate family. J. Biol. Chem. 272:21403–21407

    Article  PubMed  CAS  Google Scholar 

  89. Yenush L, White MF (1997) The IRS-signalling system during insulin and cytokine action. BioEssays 19: 491–500

    Article  PubMed  CAS  Google Scholar 

  90. Yamauchi K, Holt K, Pessin JE (1993) Phosphatidylinositol 3-kinase functions upstream of ras and raf in mediating insulin stimulation of c-fos transcription. J. biol. Chem. 268: 14597–14600

    PubMed  CAS  Google Scholar 

  91. Lam K, Carpenter CL, Ruderman NB, Friel JC, Kelly KL (1994) The phosphatidlyinositol 3 kinase serine phosphorylates IRS-1; stimulation by insulin and inhibition by wortmannin. J. Biol. Chem. 269: 20648–20652

    PubMed  CAS  Google Scholar 

  92. Pfeffer LM, Mullersman JE, Pfeffer SR, Murti A, Shi W, Yang CH (1997) STAT3 as an adaptor to couple phosphatidlyinositol 3 kinase to the IFNAR1 chain of the type 1 interferon receptor. Science 276: 1418–1420

    Article  PubMed  CAS  Google Scholar 

  93. Beitner-Johnson D, Balkesley VA, Shen-Orr Z, Jiminez M, Stannard B, Wang LM, Pierce J, LeRoith D (1996) The proto oncogene product c-Crk associates with insulin receptor substrate 1 and 4PS. J. Biol. Chem. 271: 9287–9290

    Article  PubMed  CAS  Google Scholar 

  94. Smal J, DeMeyts P (1987) Role of protein kinase C in the insulin like effects of growth hormone in rat adipocytes. Biochem. biophys. Res. Communic. 147: 1232–1240

    Article  CAS  Google Scholar 

  95. Slootweg MC, Degroot RP, Herrmann-Erlee MP, Koornneef I, Kruijer W, Kramer Ym (1991) Growth hormone induces expression of c-jun and jun B oncogenes and employs a protein kinase C signal transduction pathway for the induction of c-fos oncogene expression. J. Mol. Endocrinol. 6: 179–188

    Article  PubMed  CAS  Google Scholar 

  96. Tollet P, Legraverand C, Gustafsson JA, Mode A (1991) A role for protein kinases in the growth hormone regulation of cytochrome P4502cl2 and insulin like growth factor-1 mRNA expression in primary rat heaptocytes. Mol. Endocrinol. 5: 1351–1358

    Article  PubMed  CAS  Google Scholar 

  97. Gaur S, Yamaguchi H, Goodman HM (1996) Growth hormone increases calcium uptake in rat fat cells by a mechanism dependent on protein kinase C. Am. J. Physiol. 270:C1485–C1492

    PubMed  CAS  Google Scholar 

  98. Clarkson RW, Chen CM, Harrison S, Wells C, Muscat GE, Waters MJ (1995) Early responses of transactivating factors to growth hormone in preadipocytes. Mol Endocrinol. 9: 108–120

    Article  PubMed  CAS  Google Scholar 

  99. Dekker LV, Parker PJ (1994) Protein kinase C: a question of specificity. TIBS 19: 73–77

    PubMed  CAS  Google Scholar 

  100. Okada S, Kopchick JJ (1997) Growth hormone and insulin stimulate different subsets of protein kinase C isotypes through different mechanisms. Proc. 79th Ann. Meet. Endocrine Soc. (Abstract p576)

    Google Scholar 

  101. l00.Doglio A, Dani C, Grimaldi P, Ailhaud G (1989) Growth hormone stimulates c-fos gene expression by means of protein kinase C without increasing inositol lipid turnover. Proc. Natl. Acad. Sci. USA 86: 1148–1152

    Article  PubMed  CAS  Google Scholar 

  102. Johnson RM, Napier MA, Cronin MJ, King KL (1990) Growth hormone stimulates the formation of sn-l,2-diacylglycerol in rat heaptocytes. Endocrinology 127: 2099–2103

    Article  PubMed  CAS  Google Scholar 

  103. Rogers SA, Hammerman MR (1989) Growth hormone activates phospholipase C in proximal tubular basolateral membranes from canine kidney. Proc. Natl. Acad. Sci. USA 86: 6363–6366

    Article  PubMed  CAS  Google Scholar 

  104. Roupas P, Herington AC (1995) Signalling mechanisms involved in the production of diacylglycerol by growth hormone. Proc 77th Meet Endocrine Soc. (Abstract p345)

    Google Scholar 

  105. Argetsinger LS, Carter-Su C (1996) Mechanism of signalling by growth hormone receptor. Physiol. Rev. 76: 1089–1107

    PubMed  CAS  Google Scholar 

  106. Hondo MM, DeMeyts P, Bouchelouche P (1994) Human growth hormone increases cytosolic free calcium in cultured human IM-9 lymphocytes: a novel mechanism mechanism of growth hormone transmembrane signalling. Biochem. Biophys. Res. communie. 202: 391–397

    Article  Google Scholar 

  107. Schwartz Y, Goodman HM (1990) Refractoriness to the insulin like effects of growth hormone depends upon calcium. Endocrinology 126: 170–176

    Article  Google Scholar 

  108. Schwartz Y, Yamaguchi H, Goodman HM (1992) Growth hormone increases intracellular free calcium in rat adipocytes: correlations with actions on carbohydrate metabolism. Endocrinology 131: 772–778

    Article  PubMed  CAS  Google Scholar 

  109. Billestrup N, Bouchelouche P, Allevato G, Hondo M, Nielsen JH (1995) Growth hormone receptor C-terminal domains required for growth hormoneinduced intracellular free calcium oscillations and gene transcription. Proc. Natl. Acad. Sci. USA 92: 2725–2729

    Article  PubMed  CAS  Google Scholar 

  110. Udy GB, Towers RP, Snell RG, Wilkins RJ, Park SH, Ram PA, Waxman DJ, Davey HW (1997) Requirement of STAT5b for sexual dimorphism of body growth rates and liver gene expression. Proc. Natl. Acad. Sci. USA 94: 7239–7244

    Article  PubMed  CAS  Google Scholar 

  111. Stahl N, Farruggella T, Boulton TG, Zhong Z, Darnell JE, Yancopoulos GD (1995) Modular tyrosine based motifs in cytokine receptors specify choice of STATs and other substrates. Science 267: 1349–1353

    Article  PubMed  CAS  Google Scholar 

  112. Smit LS, Vanderkuur JA, Stimage A, Han Y, Luo G, Yu-Lee LY, Schwartz J, Carter-Su C (1997) Growth hormone induced tyrosyl phosphorylation and DNA binding activity of STAT5a and STAT5b. Endocrinology 138: 3426–3434

    Article  PubMed  CAS  Google Scholar 

  113. Lobie PE, Allevato G, Nielsen JH, Norstedt G, Billestrup N (1995) Requirement of tyrosine residues 333 and 338 of the growth hormone receptor for selected GH stimulated function. J. Biol. Chem. 270: 21745–21750

    Article  PubMed  CAS  Google Scholar 

  114. Hansen LH, Wang X, Kopchick JJ, Bouchelouche P, Nielsen JH, Galsgaard ED, Billestrup N (1996) Identification of tyrosine residues in the intracellular domain of the growth hormone receptor required for transcriptional signalling and STAT5 activation. J. Biol. Chem. 27: 12669–12673

    Google Scholar 

  115. Finbloom DS, Petricoin EF, Hackett RH, David M, Feldman GM, Igarashi KI, Fibach E, Weber MJ, Thorner MO, Silva CM, Larner AC (1994) Growth hormone and erythropoietin differentially activate DNA-binding proteins by tyrosine phosphorylation. Mol. Cell. Biol. 14: 2113–2118

    PubMed  CAS  Google Scholar 

  116. Silva CM, Lu H, Weber MJ, Thorner MO (1994) Differential tyrosine phosphorylation of JAK1, JAK2 and STAT1 by growth hormone and interferon gamma in IM-9 cells. J. Biol. Chem. 269: 27532–27539

    PubMed  CAS  Google Scholar 

  117. Luo G, Yu-Lee LY (1997) Differential activities of STAT5 at growth related versus differentiation specific promoters. Proc 79 Meet. Endocr. Soc. (Abstract p571)

    Google Scholar 

  118. Stocklin E, Wissler M, Gouilleux F, Groner B (1996) Functional interactions between STAT5 and the glucocorticoid receptor. Nature 383: 726–728

    Article  PubMed  CAS  Google Scholar 

  119. Lisanti MP, Scherer PE, Vidugiriene J, Tang ZL, Hermanowski-Vosatka A, Tu YH, Cook RF, Sargiacomo M (1994) Characterization of caveolin rich membrane domains isolated from an endothelial-rich source: Implications for human disease. J Cell Biol 126: 111–126

    Article  PubMed  CAS  Google Scholar 

  120. Lobie PE, Mertani H, Morel G, Morales-Bustos O, Norstedt G, Waters MJ (1994) Receptor mediated nuclear translocation of growth hormone. J Biol Chem 269:21330–21339

    PubMed  CAS  Google Scholar 

  121. Lobie PE, Wood TJJ, Chen CM, Waters MJ, Norstedt G (1994) Nuclear translocation and anchorage of the growth hormone receptor. J. Biol. Chem. 269:31375–31746

    Google Scholar 

  122. Stout LE, Svensson AM, Sorenson RL (1997) Prolactin regulation of islet derived INS-1 cells: characteristics and immunocytochemical analysis of STAT5 translocation. Endocrinology 138: 1592–1603

    Article  PubMed  CAS  Google Scholar 

  123. Lobie PE, Ronsin B, Silvennoinen O, Haldosen LA, Norstedt G, Morel G (1996) Constitutive nuclear localization of Janus kinases 1 and 2. Endocrinology 137: 4037–4045

    Article  PubMed  CAS  Google Scholar 

  124. Wang Y, Yu-Lee L (1996) Multiple STAT complexes nteract at the interferon regulatory factor-1 interferon gamma activation sequence in prolactin stimulated Nb2 T cells. Mol. Cell. Endocrinol. 121: 19–28

    Article  PubMed  CAS  Google Scholar 

  125. Ram PA, Waxman DJ (1997) Interaction of growth hormone activated STATs with SH2 containing phosphotyrosine Phosphatase SHP-1 and nuclear JAK2 tyrosine kinase. J. Biol. Chem. 272: 17694–17702

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Molecular and Cell Biology and Defence Medical Research Institute, National University of Singapore, 10 Kent Ridge Crescent, 119260, Singapore, Republic of Singapore

    Peter E. Lobie

Authors
  1. Peter E. Lobie
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Sahlgrenska University Hospital, Göteborg, Sweden

    Bengt-Åke Bengtsson M.D.

Rights and permissions

Reprints and permissions

Copyright information

© 1999 Springer Science+Business Media New York

About this chapter

Cite this chapter

Lobie, P.E. (1999). Signal Transduction Through the Growth Hormone Receptor. In: Bengtsson, BÅ. (eds) Growth Hormone. Endocrine Updates, vol 4. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5163-8_2

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-5163-8_2

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7351-3

  • Online ISBN: 978-1-4615-5163-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation