Interaction between Gab1 and the c-Met receptor tyrosine kinase is responsible for epithelial morphogenesis

Abstract

THE proteins Gab1 and the related DOS (for 'daughter of seven-less') each bind to substrates of tyrosine kinases like Grb2 or Corkscrew, and act in signalling pathways downstream of tyrosine kinase receptors1–3. 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 site4,5 in c-Met. Expression of Gab1 in epithelial cells is sufficient to induce the c-Met-specific activities6–9, 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.

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Weidner, K., Di Cesare, S., Sachs, M. et al. Interaction between Gab1 and the c-Met receptor tyrosine kinase is responsible for epithelial morphogenesis. Nature 384, 173–176 (1996). https://doi.org/10.1038/384173a0

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