Lin, CC orcid.org/0000-0003-3071-172X, Melo, FA, Ghosh, R et al. (6 more authors) (2012) Inhibition of Basal FGF Receptor Signaling by Dimeric Grb2. Cell, 149 (7). pp. 1514-1524. ISSN 0092-8674
Abstract
Receptor tyrosine kinase activity is known to occur in the absence of extracellular stimuli. Importantly, this ‘‘background’’ level of receptor phosphorylation is insufficient to effect a downstream response, suggesting that strict controls are present and prohibit full activation. Here a mechanism is described in which control of FGFR2 activation is provided by the adaptor protein Grb2. Dimeric Grb2 binds to the C termini of two FGFR2 molecules. This heterotetramer is capable of a low-level receptor transphosphorylation, but C-terminal phosphorylation and recruitment of signaling proteins are sterically hindered. Upon stimulation, FGFR2 phosphorylates tyrosine residues on Grb2, promoting dissociation from the receptor and allowing full activation of downstream signaling. These observations establish a role for Grb2 as an active regulator of RTK signaling.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) > Mechanistic Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 09 Sep 2019 14:52 |
Last Modified: | 09 Sep 2019 14:52 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.cell.2012.04.033 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:129413 |