A MULTIFUNCTIONAL DOCKING SITE MEDIATES SIGNALING AND TRANSFORMATION BY THE HEPATOCYTE GROWTH-FACTOR SCATTER FACTOR-RECEPTOR FAMILY

被引：904

作者：

PONZETTO, C ^{[1
]}

BARDELLI, A ^{[1
]}

ZHEN, Z ^{[1
]}

MAINA, F ^{[1
]}

DALLAZONCA, P ^{[1
]}

GIORDANO, S ^{[1
]}

GRAZIANI, A ^{[1
]}

PANAYOTOU, G ^{[1
]}

COMOGLIO, PM ^{[1
]}

机构：

[1] LUDWIG INST CANC RES, LONDON W1P 8BT, ENGLAND

来源：

CELL | 1994年 / 77卷 / 02期

关键词：

D O I：

10.1016/0092-8674(94)90318-2

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Signaling by tyrosine kinase receptors is mediated by selective interactions between individual Src homology 2 (SH2) domains of cytoplasmic effecters 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 C gamma, pp60(c-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.

引用

页码：261 / 271

页数：11

共 55 条

[1]

BARDELLI A, 1992, ONCOGENE, V7, P1973

[2]

BHARGAVA M, 1992, CELL GROWTH DIFFER, V3, P11

[3] IDENTIFICATION OF THE HEPATOCYTE GROWTH-FACTOR RECEPTOR AS THE C-MET PROTOONCOGENE PRODUCT [J].