SILENCING OF THE EPIDERMAL GROWTH-FACTOR RECEPTOR IN THE ABSENCE OF THE LIGAND REQUIRES PHOSPHOLIPASE-C ACTIVITY

The possible involvement of phospholipase C beta (PLC beta) in a cross talk mechanism between G-protein coupled receptors and receptor tyrosi ne kinases was investigated in HeLa-S3 and A-431 cells. A basic activi ty 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 bot h cell lines, suggesting that PLC activity is necessary for the silenc ing of the EGF receptor in the absence of its ligand. Activation of PL C beta and protein kinase C (PKC) via G-protein-linked ATP receptors g reatly 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-prot ein-linked receptor and a receptor tyrosine kinase, involving signalli ng via PLC beta and PKC to a downstream protein tyrosine phosphatase f unctioning in the control of EGF receptor activity.