Silencing of the epidermal growth factor receptor in the absence of the ligand requires phospholipase C activity

AbstractThe possible involvement of phospholipase Cβ (PLCβ) in a crosstalk mechanism between G-protein coupled receptors and receptor tyrosine kinases was investigated in HeLa-S3 and A-431 cells. A basic activity of the receptor for epidermal growth factor (EGF) in the absence of its ligand was found only in A-431 cells overexpressing this receptor. Inhibition of PLC drastically increased EGF receptor activity in both cell lines, suggesting that PLC activity is necessary for the silencing of the EGF receptor in the absence of its ligand. Activation of PLCβ and protein kinase C (PKC) via G-protein-linked ATP receptors greatly diminished the basic EGF receptor activity in A-431 cells. This negative regulation was prevented by the protein tyrosine phosphatase inhibitor, vanadate. The results suggest a crosstalk between a G-protein-linked receptor and a receptor tyrosine kinase, involving signalling via PLCβ and PKC to a downstream protein tyrosine phosphatase functioning in the control of EGF receptor activity