TY - JOUR
T1 - A multifunctional docking site mediates signaling and transformation by the hepatocyte growth factor/scatter factor receptor family
AU - Ponzetto, Carola
AU - Bardelli, Alberto
AU - Zhen, Zhu
AU - Maina, Flavio
AU - dalla Zonca, Paolo
AU - Giordano, Silvia
AU - Graziani, Andrea
AU - Panayotou, George
AU - Comoglio, Paolo M.
PY - 1994/4/22
Y1 - 1994/4/22
N2 - 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.
AB - 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.
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U2 - 10.1016/0092-8674(94)90318-2
DO - 10.1016/0092-8674(94)90318-2
M3 - Article
C2 - 7513258
AN - SCOPUS:0028351702
VL - 77
SP - 261
EP - 271
JO - Cell
JF - Cell
SN - 0092-8674
IS - 2
ER -