Weidner K M, Di Cesare S, Sachs M, Brinkmann V, Behrens J, Birchmeier W
Max Delbrück Center for Molecular Medicine, Berlin, Germany.
Nature. 1996 Nov 14;384(6605):173-6. doi: 10.1038/384173a0.
The proteins Gab1 and the related DOS (for 'daughter of sevenless') each bind to substrates of tyrosine kinases like Grb2 or Corkscrew, and act in signalling pathways downstream of tyrosine kinase receptors. Here we show that Gab1 interacts directly with the c-met-encoded receptor tyrosine kinase but not with a number of other tyrosine kinases from different subfamilies. A newly identified proline-rich domain of Gab1 is responsible for the binding of this protein to the tyrosine-phosphorylated bidentate docking site in c-Met. Expression of Gab1 in epithelial cells is sufficient to induce the c-Met-specific activities, including branching morphogenesis. Thus we have discovered a new phosphotyrosine interaction domain in Gab1 and shown that Gab1 is the substrate of the c-Met receptor tyrosine kinase that mediates epithelial morphogenesis.
蛋白质Gab1以及相关的DOS（“sevenless的子代”）各自与诸如Grb2或Corkscrew等酪氨酸激酶的底物结合，并在酪氨酸激酶受体下游的信号通路中发挥作用。我们在此表明，Gab1直接与c-met编码的受体酪氨酸激酶相互作用，但不与来自不同亚家族的许多其他酪氨酸激酶相互作用。Gab1新鉴定的富含脯氨酸结构域负责该蛋白质与c-Met中酪氨酸磷酸化的双齿对接位点的结合。Gab1在上皮细胞中的表达足以诱导c-Met特异性活性，包括分支形态发生。因此，我们在Gab1中发现了一个新的磷酸酪氨酸相互作用结构域，并表明Gab1是介导上皮形态发生的c-Met受体酪氨酸激酶的底物。
