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Grb2-independent recruitment of Gab1 requires the C-terminal lobe and structural integrity of the Met receptor kinase domain

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dc.contributor.author Lock, L. S. en_US
dc.contributor.author Frigault, M. M. en_US
dc.contributor.author Saucier, C. en_US
dc.contributor.author Park, M. en_US
dc.date.accessioned 2006-06-22T14:16:48Z
dc.date.available 2006-06-22T14:16:48Z
dc.date.issued 2003-08 en_US
dc.identifier.citation J Biol Chem 278, 30083-90 (2003) en_US
dc.identifier.uri http://hdl.handle.net/1807.1/181
dc.description This article is hosted on a website external to the CBCRA Open Access Archive. Selecting “View/Open” below will launch the full-text article in another browser window.
dc.description.abstract The Gab1 docking protein forms a platform for the assembly of a multiprotein signaling complex downstream from receptor tyrosine kinases. In general, recruitment of Gab1 occurs indirectly, via the adapter protein Grb2. In addition, Gab1 interacts with the Met/hepatocyte growth factor receptor in a Grb2-independent manner. This interaction requires a Met binding domain (MBD) in Gab1 and is essential for Met-mediated epithelial morphogenesis. The Gab1 MBD has been proposed to act as a phosphotyrosine binding domain that binds Tyr-1349 in the Met receptor. We show that a 16-amino acid motif within the Gab1 MBD is sufficient for interaction with the Met receptor, suggesting that it is unlikely that the Gab1 MBD forms a structured domain. Alternatively, the structural integrity of the Met receptor, and residues upstream of Tyr-1349 located in the C-terminal lobe of the kinase domain, are required for Grb2-independent interaction with the Gab1 MBD. Moreover, the substitution of Tyr-1349 with an acidic residue allows for the recruitment of the Gab1 MBD and for phosphorylation of Gab1. We propose that Gab1 and the Met receptor interact in a novel manner, such that the activated kinase domain of Met and the negative charge of phosphotyrosine 1349 engage the Gab1 MBD as an extended peptide ligand. en_US
dc.description.provenance Made available in DSpace on 2006-06-22T14:16:48Z (GMT). No. of bitstreams: 1 Lock.2003.30083.html: 415 bytes, checksum: a1db30461c4d384c026ba6555c40b019 (MD5) Previous issue date: 2003-08 en
dc.format.extent 415 bytes
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dc.language.iso en en_US
dc.publisher American Society for Biochemistry and Molecular Biology en_US
dc.relation.uri http://www.asbmb.org/ en_US
dc.title Grb2-independent recruitment of Gab1 requires the C-terminal lobe and structural integrity of the Met receptor kinase domain en_US
dc.type Article en_US

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