Details

Autor(en) / Beteiligte

• Timsah, Zahra
• Ahmed, Zamal
• Lin, Chi-Chuan
• Melo, Fernando A
• Stagg, Loren J
• Leonard, Paul G
• Jeyabal, Prince
• Berrout, Jonathan
• O'Neil, Roger G
• Bogdanov, Mikhail
• Ladbury, John E

Titel

Competition between Grb2 and Plcγ1 for FGFR2 regulates basal phospholipase activity and invasion

Ist Teil von

• Nature structural & molecular biology, 2014-02, Vol.21 (2), p.180-188

Ort / Verlag

United States

Erscheinungsjahr

2014

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.