Figure 7: Schematic representation of the potential mechanism by which 2-O-Bn-InsP5 inhibits the PDK1-dependent PLCγ1 activation.
From: A Small Molecule Inhibitor of PDK1/PLCγ1 Interaction Blocks Breast and Melanoma Cancer Cell Invasion
EGF induces phosphorylation of EGF receptor and activation of PI3Ks which catalyse the synthesis of PtdIns(3,4,5)P3 (PIP3). PIP3 in turn recruits the protein complex PDK1/PLCγ1 to the plasma membrane where PLCγ1 is activated in a mechanism involving phosphorylation of its residue Tyr783. Recruitment of the protein complex and PLCγ1 activation stimulate cell migration, invasion and metastasis dissemination. By competing with PIP3 for the binding to PDK1 PH domain, 2-O-Bn-InsP5 prevents the formation of PDK1/PLCγ1 complex and the recruitment of both proteins to the plasma membrane. Thus 2-O-Bn-InsP5 inhibits PLCγ1 phosphorylation and activity and reduces tumour cell migration and metastasis dissemination. Yellow dots are phosphate groups bound to the inositol ring.
