Interaction between Gab1 and the c-Met receptor tyrosine kinase is responsible for epithelial morphogenesis.
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.
Max Delbrück Center for Molecular Medicine, Berlin, Germany.
K M
KM
Weidner
S
S
Di Cesare
M
M
Sachs
V
V
Brinkmann
J
J
Behrens
W
W
Birchmeier
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D004848:Epithelium / Q000196:embryology; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009024:Morphogenesis / Q000502:physiology*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011233:Precipitin Tests; D011392:Proline / Q000378:metabolism; D011485:Protein Binding; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae; D015398:Signal Transduction; D013379:Substrate Specificity
D048868:Adaptor Proteins, Signal Transducing; C098587:GAB1 protein, human; C490897:Gab1 protein, mouse; D010750:Phosphoproteins; D011993:Recombinant Fusion Proteins; D011392:Proline; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases