Distinct Effects of Na⁺ and Li⁺ on the Induction of Morphological Changes in A431 Cells Mediated by Epidermal Growth Factor

Abstract

Epidermal growth factor (EGF) induced the formation of thin sheetlike extensions (lamellipodia) and filamentous extensions at the edges of colonies of A431 cells. To determine the necessary processes for the induction of the morphological changes mediated by EGF, the effects of a variety of ions on these changes were examined. In a NaCl solution supplemented with CaCl₂, MgCl₂ and glucose, no EGF-induced morphological changes were observed. However, when the NaCl was replaced with LiCl, fingerlike extensions were formed, but sheetlike extensions were not. Addition of vanadate to the NaCl solution also induced fingerlike extensions in cells treated with EGF. In contrast, sheetlike lamellipodia were formed in EGF-treated cells by the addition of K⁺ or PO₄^3-to the NaCl solution or by the addition of PO₄^3- to the LiCl solution. These findings indicate that Li⁺, K⁺, PO₄^3- and vanadate are involved in the processes of EGF-induced morphological changes. Since vanadate and Li⁺ have been shown to inhibit phosphatases, an EGF-dependent phosphorylation step may play an important role in the induction of the morphological changes observed.