Related Experiment Video

Updated: May 3, 2026

A High-content Imaging Workflow to Study Grb2 Signaling Complexes by Expression Cloning
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A High-content Imaging Workflow to Study Grb2 Signaling Complexes by Expression Cloning

Published on: October 30, 2012

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

Zahra Timsah1, Zamal Ahmed2, Chi-Chuan Lin1

  • 1Department of Biochemistry and Molecular Biology, University of Texas, M.D. Anderson Cancer Center, Houston, Texas, USA.

Nature Structural & Molecular Biology
|January 21, 2014
PubMed

Insights

Low Grb2 adaptor protein levels in FGFR2 cancer cells promote metastasis. Plcγ1 binding to FGFR2 increases cell motility and invasion, driven by competition for a receptor site.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Fibroblast Growth Factor Receptor 2 (FGFR2) is implicated in cancer progression.
  • The adaptor protein Grb2 plays a role in receptor signaling.
  • Phospholipase C gamma 1 (Plcγ1) is involved in cellular signaling pathways.

Purpose of the Study:

  • To investigate the role of Grb2 concentration in FGFR2-mediated cancer cell metastasis.
  • To elucidate the mechanism of Plcγ1 recruitment to FGFR2 in nonstimulated cells.
  • To understand the signaling events leading to increased cell motility and invasion.

Main Methods:

  • Analysis of FGFR2-expressing human cancer cells with varying Grb2 concentrations.
  • Investigation of protein-protein interactions at the C terminus of FGFR2.
  • Measurement of phospholipase activity, phosphatidylinositol 4,5-bisphosphate turnover, and intracellular calcium levels.

Main Results:

  • Reduced Grb2 concentration correlates with a higher prevalence of metastatic outcome.
  • In nonstimulated cells, Plcγ1 competes with Grb2 for a binding site on FGFR2.
  • Plcγ1 recruitment upregulates phospholipase activity, increasing cell motility and invasion.

Conclusions:

  • Metastasis in FGFR2-expressing cancers can be driven by the competition between Grb2 and Plcγ1 for FGFR2.
  • This competition occurs at a phosphorylation-independent binding site.
  • The findings reveal a novel mechanism regulating cancer cell invasiveness.

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