A multifunctional docking site mediates signaling and transformation by the hepatocyte growth factor/scatter factor receptor family

Carola Ponzetto, Alberto Bardelli, Zhu Zhen, Flavio Maina, Paolo dalla Zonca, Silvia Giordano, Andrea Graziani, George Panayotou, Paolo M. Comoglio

Research output: Contribution to journalArticle

Abstract

Signaling by tyrosine kinase receptors is mediated by selective interactions between individual Src homology 2 (SH2) domains of cytoplasmic effectors and specific phosphotyrosine residues in the activated receptor. Here, we report the existence in the hepatocyte growth factor/scatter factor ( HGF SF) receptor of a multifunctional docking site made of the tandemly arranged degenerate sequence YVH NV. Phosphorylation of this site mediates intermediate- to high-affinity interactions with multiple SH2-containing signal transducers, including phosphatidylinositol 3-kinase, phospholipase Cγ, pp60c-src, and the GRB-2-Sos complex. Mutation of the two tyrosines results in loss of biological function, as shown by abrogation of the transforming activity in the oncogenic counterpart of the receptor. The same bidentate motif is conserved in the evolutionarily related receptors Sea and Ron, suggesting that in all members of the HGF SF receptor family, signal transduction is channeled through a multifunctional binding site.

Original languageEnglish
Pages (from-to)261-271
Number of pages11
JournalCell
Volume77
Issue number2
DOIs
Publication statusPublished - Apr 22 1994

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Proto-Oncogene Proteins c-met
Hepatocyte Growth Factor
Phosphatidylinositol 3-Kinase
Signal transduction
Phosphotyrosine
Phosphorylation
src Homology Domains
Receptor Protein-Tyrosine Kinases
Type C Phospholipases
Transducers
Oceans and Seas
Tyrosine
Signal Transduction
Binding Sites
Mutation

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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A multifunctional docking site mediates signaling and transformation by the hepatocyte growth factor/scatter factor receptor family. / Ponzetto, Carola; Bardelli, Alberto; Zhen, Zhu; Maina, Flavio; dalla Zonca, Paolo; Giordano, Silvia; Graziani, Andrea; Panayotou, George; Comoglio, Paolo M.

In: Cell, Vol. 77, No. 2, 22.04.1994, p. 261-271.

Research output: Contribution to journalArticle

Ponzetto, Carola ; Bardelli, Alberto ; Zhen, Zhu ; Maina, Flavio ; dalla Zonca, Paolo ; Giordano, Silvia ; Graziani, Andrea ; Panayotou, George ; Comoglio, Paolo M. / A multifunctional docking site mediates signaling and transformation by the hepatocyte growth factor/scatter factor receptor family. In: Cell. 1994 ; Vol. 77, No. 2. pp. 261-271.
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AU - Giordano, Silvia

AU - Graziani, Andrea

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