Glial cell line-derived nenrotrophic factor (GDNF) stimulates ret activity

Francesca Carlomagno, Rosa Marina Melillo, Giuliana Salvatore, Roberta Visconti, Gabriella De Vita, Gelsy Lupoli, Michèle Marinaccio, Massimo Santoro, Giancarlo Vecchio, Alfredo Fusco

Research output: Contribution to journalArticlepeer-review


Ret is a receptor-like tyrosine kinase involved in several neoplastic and developmental diseases affecting thyroid gland and tissues of neuroectodermal origin. Rearrangements of the ret gene are observed in a sizeable fraction of human thyroid papillary carcinomas. «Gain of function» of ret has been shown to be caused by mutations associated with multiple endocrine neoplasia type 2A (MEN2A) or 2B (MEN2B) syndromes. Conversely, congenital megacolon or Hirschsprung's disease (HSCR) is associated with «loss of function» of ret. Here, we show that glial cell line-derived neurotrophic factor (GDNF), a member of the TGFβ super-family, is able to stimulate in vivo tyrosine kinase activity of Ret. These effects were specific to GDNF, since neither other members of the TGFβ family nor other neurotrophins and unrelated growth factors exerted the same effects. Consistently, ectopic expression of Ret in NIH 3T3 cells rendered them responsive to the mitogenic action of GDNF. These results allow the conclusion that GDNF is a functional ligand for Ret and suggest that Ret-GDNF interaction plays an important role in the pathogenesis of diseases associated with ret mutations.

Original languageEnglish
Pages (from-to)139-149
Number of pages11
JournalRendiconti Lincei
Issue number2
Publication statusPublished - Jun 1997


  • Ligand
  • Neurotrophin
  • Transformation
  • Tyrosine kinase

ASJC Scopus subject areas

  • Engineering(all)


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