Timsah, Z, Ahmed, Z, Lin, CC orcid.org/0000-0003-3071-172X et al. (8 more authors) (2014) Competition between Grb2 and Plcγ1 for FGFR2 regulates basal phospholipase activity and invasion. Nature Structural and Molecular Biology, 21 (2). pp. 180-188. ISSN 1545-9993
Abstract
FGFR2-expressing human cancer cells with low concentrations of the adaptor protein Grb2 show high prevalence for metastatic outcome. In nonstimulated cells, the SH3 domain (and not the SH2 domains) of Plcγ1 directly competes for a binding site at the very C terminus of FGFR2 with the C-terminal SH3 domain of Grb2. Reduction of Grb2 concentration permits Plcγ1 access to the receptor. Recruitment of Plcγ1 in this way is sufficient to upregulate phospholipase activity. This results in elevated phosphatidylinositol 4,5-bisphosphate turnover and intracellular calcium levels, thus leading to increased cell motility and promotion of cell-invasive behavior in the absence of extracellular receptor stimulation. Therefore, metastatic outcome can be dictated by the constitutive competition between Grb2 and Plcγ1 for the phosphorylation-independent binding site on FGFR2.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Keywords: | Binding Sites; Binding, Competitive; Cell Line, Tumor; GRB2 Adaptor Protein; HEK293 Cells; Humans; Models, Genetic; Neoplasm Invasiveness; Phospholipase C gamma; Phospholipases; Protein Structure, Tertiary; Receptor, Fibroblast Growth Factor, Type 2 |
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: | 17 Aug 2015 13:55 |
Last Modified: | 04 Dec 2020 13:04 |
Published Version: | http://dx.doi.org/10.1038/nsmb.2752 |
Status: | Published |
Publisher: | Nature Publishing Group |
Identification Number: | 10.1038/nsmb.2752 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:86703 |