Competition between Grb2 and Plcγ1 for FGFR2 regulates basal phospholipase activity and invasion
| Autor: | Chi-Chuan Lin, Zamal Ahmed, Zahra Timsah, Prince Jeyabal, Fernando A. Melo, Jonathan Berrout, Roger G. O'Neil, Paul G. Leonard, John E. Ladbury, Loren J. Stagg, Mikhail Bogdanov |
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| Rok vydání: | 2014 |
| Předmět: |
Phospholipase
SH2 domain Binding Competitive SH3 domain chemistry.chemical_compound Structural Biology Cell Line Tumor Extracellular Humans Neoplasm Invasiveness Phosphatidylinositol Receptor Fibroblast Growth Factor Type 2 Binding site Molecular Biology GRB2 Adaptor Protein Binding Sites Models Genetic biology Phospholipase C gamma Signal transducing adaptor protein Protein Structure Tertiary Cell biology HEK293 Cells chemistry Phospholipases biology.protein GRB2 biological phenomena cell phenomena and immunity |
| Zdroj: | Nature Structural & Molecular Biology. 21:180-188 |
| ISSN: | 1545-9985 1545-9993 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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