Skip to main content
SpringerLink
Log in

Signal Transduction by the Receptor Tyrosine Kinase Ret

  • Conference paper
Book cover Genes and Environment in Cancer

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 154))

Abstract

Ret is the receptor for glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN). Defects in this receptor underlie several genetic syndromes. The receptor is a transmembrane tyrosine kinase which transduces Ret-mediated signaling to a variety of signaling pathways, most notably the Ras signlaing pathway and the phosphatidylinositol-3 kinase pathway. These pathways are activated through the interaction of adaptor proteins to tyrosine phosphorylated receptor. The ultimate biological effects, depending on the cell type, include morphological changes in the cytoskeleton, cell scattering, proliferation, and differentiation.

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

Access this chapter

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 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight 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

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Asai N, Murakami H, Iwashita T, Takahashi M (1996) A mutation at tyrosine 1062 in MEN2A-RET and MEN2B-Ret impairs their transforming activity and association with Shc adaptor proteins. J Biol Chem 271: 17644–17649

    Article  PubMed  CAS  Google Scholar 

  • Avruch J, Zhang XF, Kyriakis JM (1994) Raf meets Ras: completing the framework of a signal transduction pathway. Trends Biochem Sci 19: 279–283

    Article  PubMed  CAS  Google Scholar 

  • Bentley D, Toroian-Raymond A (1986) Disoriented pathfinding by pioneer neurone growth cones deprived of filopodia by cytochalasin treatment. Nature 323: 712–715

    Article  PubMed  CAS  Google Scholar 

  • Bork P, Margolis B: A phosphotyrosine interaction domain. Cell 80: 693–694

    Google Scholar 

  • Borrello MG, Pelicci G, Arighi E, De Filippis L, Greco A, Bongarzone I, Rizzetti MG, Pelicci PG, Pierotti MA (1994) The oncogenic versions of the Ret and Trk tyrosine kinases bind Shc and Grb2 adaptor proteins. Oncogene 9: 1661–1668

    PubMed  CAS  Google Scholar 

  • Borrello MG, Alberti L, Arighi E, Bongarzone I, Battistini C, Bardelli A, Pasini B, Piutti C, Rizzetti MG, Mondellini P, Radice MT, Pierotti MA (1996) The full oncogenic activity of Ret/ptc2 depends on tyrosine 539, a docking site for phospholipase C-gamma. Mol Cell Biol 16: 2151–2163

    PubMed  CAS  Google Scholar 

  • Bos JL (1995) A target for phosphoinositide 3-kinase: Akt/PKB. Trends Biochem Sci 20: 441–442

    Article  PubMed  CAS  Google Scholar 

  • Buj-Bello A, Adu J, Pinon LG, Horton A, Thompson J, Rosenthal A, Chinchetru M, Buchman VL, Davies AM (1997) Neurturin responsiveness requires a GPI-linked receptor and the Ret receptor tyrosine kinase. Nature 387: 721–724

    Article  PubMed  CAS  Google Scholar 

  • Califano D, Monaco C, De Vita G, D’Alessio A, Dathan NA, Possenti R, Vecchio G, Fusco A, Santoro M, de Franciscis V (1995) Activated RET/PTC oncogene elicts immediate early and delayed response genes in PC12 cells. Oncogene 11: 107–112

    PubMed  CAS  Google Scholar 

  • Durbec PL, Marcos-Gutierrez CV, Kilkenny C, Grigoriou M, Wartiowaara K, Suvanto P, Smith D, Ponder BAI, Costantini F, Saarma M, Sariola H, Pachnis V (1996) GDNF signalling through the Ret receptor tyrosine kinase. Nature 381: 789–793

    Article  PubMed  CAS  Google Scholar 

  • Durick K, Yao VJ, Borrello MG, Bongarzone I, Pierotti MA, Taylor SS (1995) Tyrosines outside the kinase core and dimerization are required for the mitogenic activity of RET/ ptc2. J Biol Chem 270: 24642–24645

    Article  PubMed  CAS  Google Scholar 

  • Durick K, Wu R-Y, Gill GN, Taylor SS (1996) Mitogenic signaling by Ret/ptc2 requires association with Enigma via a LIM domain. J Biol Chem 271: 12691–12694

    Article  PubMed  CAS  Google Scholar 

  • Feig LA, Urano T, Cantor S (1996) Evidence for a Ras/Ral signaling cascade. Trends Biochem Sci 21: 438–441

    Article  PubMed  CAS  Google Scholar 

  • Forscher P, Smith SJ (1988) Actions of cytochalasins on the organization of actin filaments and microtubules in a neuronal growth cone. J Cell Biol 107: 1505–1516

    Article  PubMed  CAS  Google Scholar 

  • Grieco D, Santoro M, Dathan NA, Fusco A (1995) Activated RET oncogene products induce maturation of Xenopus oocytes. Oncogene 11: 113–117

    PubMed  CAS  Google Scholar 

  • Heldin CH (1995) Dimerization of cell surface receptors in signal transduction. Cell 80: 213–223

    Article  PubMed  CAS  Google Scholar 

  • Iwashita T, Asai N, Murakami H, Matsuyama M, Takahashi M (1996) Identification of tyrosine residues that are essential for transforming activity of the ret proto-oncogene with MEN2A or MEN2B mutations. Oncogene 12: 481–487

    PubMed  CAS  Google Scholar 

  • Jing S, Wen D, Yu Y, Holst PL, Luo Y, Fang M, Tamir R, Antonio L, Hu Z, Cupples R, Louis J-C, Hu S, Altrock BW, Fox GM (1996) GDNF-induced activation of the Ret protein tyrosine kinase is mediated by GDNFR-alpha, a novel receptor for GDNF. Cell 85: 1113–1124

    Article  PubMed  CAS  Google Scholar 

  • Kimura K, Hattori S, Kabuyama Y, Shizawa Y, Takayanagi J, Nakamura S, Toki S, Matsuda Y, Onodera K, Fukui Y (1994) Neurite outgrowth of PC12 cells is suppressed by wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase. J Biol Chem 269: 18961–18967

    PubMed  CAS  Google Scholar 

  • Klein RD, Sherman D, Ho WH, Stone D, Bennett GL, Moffat B, Vandlen R, Simmons L, Gu Q, Hongo JA, Devaux B, Poulsen K, Armanini M, Nozaki C, Asai N, Goddard A, Phillips H, Henderson CE, Takahashi M, Rosenthal A (1997) A GPI-linked protein that interacts with Ret to form a candidate neurturin receptor. Nature 387: 717–721

    Article  PubMed  CAS  Google Scholar 

  • Kotzbauer PT, Lampe PA, Heuckeroth RO, Golden JP, Creedon DJ, Johnson EM Jr, Milbrandt J (1996) Neurturin, a relative of glial-cell-line-derived neurotrophic factor. Nature 384: 467–470

    Article  PubMed  CAS  Google Scholar 

  • Lemmon MA, Schlessinger J (1994) Regulation of signal transduction and signal diversity by receptor oligomerization. Trends Biochem Sci 19: 459–463

    Article  PubMed  CAS  Google Scholar 

  • Liu X, Vega QC, Decker RA, Pandey A, Worby CA, Dixon JE (1996) Oncogenic Ret receptors display different autophosphorylation sites and substrate binding specificities. J Biol Chem 271: 5309–5312

    Article  PubMed  CAS  Google Scholar 

  • Marshall CJ (1995) Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation. Cell 80: 179–185

    Article  PubMed  CAS  Google Scholar 

  • Newgreen D, Gibbins I (1982) Factors controlling the time of onset of the migration of neural crest cells in the fowl embryo. Cell Tissue Res 224: 145–160

    Article  PubMed  CAS  Google Scholar 

  • Ooi J, Yajnik V, Immanuel D, Gordon M, Moskow JJ, Buchberg AM, Margolis B (1995) The cloning of Grb10 reveals a new family of SH2 domain proteins. Oncogene 10: 1621–1630

    PubMed  CAS  Google Scholar 

  • Pandey A, Duan H, Di Fiore PP, Dixit VM (1995) The Ret receptor protein tyrosine kinase associates with the SH2-containing adapter protein GrblO. J Biol Chem 270: 21461–21463

    Article  PubMed  CAS  Google Scholar 

  • Rodriguez-Viciana P, Warne PH, Dhand R, Vanhaesebroeck B, Gout I, Fry MJ, Waterfield MD, Downward J (1994) Phosphatidylinositol-3-OH kinase as a direct target of Ras. Nature 370: 527–532

    Article  PubMed  CAS  Google Scholar 

  • Rodriguez-Viciana P, Warne PH, Vanhaesebroeck B, Waterfield MD, Downward J (1996) Activation of phosphoinsitide 3-kinase by interaction with Ras and by point mutation. EMBO J 15: 2442–2451

    PubMed  CAS  Google Scholar 

  • Romano A, Wong WT, Santoro M, Wirth PJ, Thorgeirsson SS, Di Fiore PP (1994) The high transforming potency of erbB-2 and ret is associated with phosphorylation of paxillin and a 23 kDa protein. Oncogene 9: 2923–2933

    PubMed  CAS  Google Scholar 

  • Santoro M, Wong WT, Aroca P, Santos E, Matoskova B, Grieco M, Fusco A, Di Fiore PP (1994) An epidermal growth factor receptor/ret chimera generates mitogenic and transforming signals: evidence for a ret-specific signaling pathway. Mol Cell Biol 14: 663–675

    PubMed  CAS  Google Scholar 

  • Symons M (1996) Rho family GTPases: the cytoskeleton and beyond. Trends Biochem Sci 21: 178–181

    PubMed  CAS  Google Scholar 

  • Treanor JJS, Goodman L, De Sauvage F, Stone DM, Poulsen KT, Beck CD, Gray C, Armanini MP, Pollock RA, Hefti F, Phillips HS, Goddard A, Moore MW, Buj Bello A, Davies AM, Asai N, Takahashi M, Vandlen R, Henderson CE, Rosenthal A (1996) Characterization of a multicomponent receptor for GDNE. Nature 382: 80–83

    Article  PubMed  CAS  Google Scholar 

  • Ullrich A, Schlessinger J (1990) Signal transduction by receptors with tyrosine kinase activity. Cell 61: 203–212

    Article  PubMed  CAS  Google Scholar 

  • Umbhauer M, Marshall CJ, Mason CS, Old RW, Smith JC (1995) Mesoderm induction in Xenopus caused by activation of MAP kinase. Nature 376: 58–62

    Article  PubMed  CAS  Google Scholar 

  • van der Geer P, Wiley S, Ka-Man Lai V, Olivier JP, Gish GD, Stephens R, Kaplan D, Shoelson S, Pawson T (1995) A conserved amino-terminal Shc domain binds to phosphotyrosine motifs in activated receptors and phosphopeptides. Curr Biol 5: 404–412

    Article  PubMed  Google Scholar 

  • van Puijenbroek AAFL, van Weering DHJ, van den Brink CE, Bos JL, van der Saag PT, de Laat SW, den Hertog J (1997) Cell scattering of SK-N-MC neuroepithelioma cells in response to Ret and FGF receptor tyrosine kinase activation is correlated with sustained ERK2 activation. Oncogene 14: 1147–1158

    Google Scholar 

  • van Weering DHJ, Medema JP, van Puijenbroek A, Burgering BMT, Baas PD, Bos JL (1995) Ret receptor tyrosine kinase activates extracellular signal-regulated kinase 2 in SK-N-MC cells. Oncogene 11: 2207–2214

    PubMed  Google Scholar 

  • van Weering DHJ, Bos JL (1997) Glial cell line-derived neurotrophic factor induces Retmediated lamellipodia formation. J Biol Chem 272: 249–254

    Article  PubMed  Google Scholar 

  • Wu RY, Gill GN (1994) LIM domain recognition of a tyrosine-containing tight turn. J Biol Chem 269: 25085–25090

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory for Physiological Chemistry, Utrecht University, P.O. Box 80042, 3508 TA, Utrecht, The Netherlands

    D. H. J. van Weering & J. L. Bos

Authors
  1. D. H. J. van Weering
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. L. Bos
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Abteilung Zytogenetik, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D-69120, Heidelberg, Germany

    Manfred Schwab

  2. Pathologisches Institut, Universität München, Thalkirchner Straße 36, D-80377, München, Germany

    Hartmut M. Rabes

  3. Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D-69120, Heidelberg, Germany

    Klaus Munk

  4. Max-Planck-Institut für Biochemie, Am Klopferspitz 18a, D-82152, Martinsried, Germany

    Hans Peter Hofschneider

Rights and permissions

Reprints and permissions

Copyright information

© 1998 Springer-Verlag Berlin · Heidelberg

About this paper

Cite this paper

van Weering, D.H.J., Bos, J.L. (1998). Signal Transduction by the Receptor Tyrosine Kinase Ret. In: Schwab, M., Rabes, H.M., Munk, K., Hofschneider, H.P. (eds) Genes and Environment in Cancer. Recent Results in Cancer Research, vol 154. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-46870-4_18

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-46870-4_18

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-46872-8

  • Online ISBN: 978-3-642-46870-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation