Disabled is a putative adaptor protein that functions during signaling by the sevenless receptor tyrosine kinase.
DRK, the Drosophila homolog of the SH2-SH3 domain adaptor protein Grb2, is required during signaling by the sevenless receptor tyrosine kinase (SEV). One role of DRK is to provide a link between activated SEV and the Ras1 activator SOS. We have investigated the possibility that DRK performs other functions by identifying additional DRK-binding proteins. We show that the phosphotyrosine-binding (PTB) domain-containing protein Disabled (DAB) binds to the DRK SH3 domains. DAB is expressed in the ommatidial clusters, and loss of DAB function disrupts ommatidial development. Moreover, reduction of DAB function attenuates signaling by a constitutively activated SEV. Our biochemical analysis suggests that DAB binds SEV directly via its PTB domain, becomes tyrosine phosphorylated upon SEV activation, and then serves as an adaptor protein for SH2 domain-containing proteins. Taken together, these results indicate that DAB is a novel component of the SEV signaling pathway.
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Department of Biological Sciences, Stanford University, Stanford, California 94305-5020, USA.
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D000818:Animals; D002460:Cell Line; D004330:Drosophila / Q000378:metabolism; D029721:Drosophila Proteins; D005136:Eye Proteins / Q000378:metabolism*; D019476:Insect Proteins / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011392:Proline; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism; D018909:src Homology Domains
D029721:Drosophila Proteins; D005136:Eye Proteins; D019476:Insect Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C080216:dab protein, Drosophila; C080530:drk protein, Drosophila; D014443:Tyrosine; D011392:Proline; D020794:Receptor Protein-Tyrosine Kinases; C056737:sev protein, Drosophila