Kannazuki Seminar “Cell signaling and oncogenesis in the absence of growth factor stimulation”

Place Institute for Protein Research, 4F Seminar Room
Date Tuesday, 6 October 2015, 15:00-


Speaker:Prof. John E. LadburySchool of Cellular and Molecular Biology, University of Leeds, UK

FGFR2-expressing cancer cells with low concentrations of the adaptor protein Grb2 show high prevalence for metastatic outcome. In non-stimulated cells the SH3 domain (and not the SH2 domain(s)) 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 access by Plcγ1 to the receptor. Recruitment of Plcγ1 in this way is sufficient to up-regulate phospholipase activity. This results in 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.