Abstract
Lowering of extracellular Ca^2+^ levels will reversibly arrest the growth of human fibroblasts (WI38). Simian virus~40~(SV~40~)‐transformed WI38 cells do not exhibit this Ca^2+^‐dependent arrest. One possibility for this difference in Ca^2+^ requirement is that extracellular or surface membrane‐bound Ca^2+^ may be required for growth factor receptor‐mediated endocytosis and this Ca^2+^ requirement may differ in normal versus transformed cells. In this study we have evaluated the role of Ca^2+^ in the binding, internalization, and degradation of epidermal growth factor (EGF) in the WI38 and SV~40~ WI38 cell. The binding of [^125^I]EGF to the cell surface is not significantly altered by lowering of Ca^2+^ to 10^−5^‐M levels in either the normal or transformed cell. At this Ca^2+^ level, growth of the normal cell is inhibited. The subsequent internalization of EGF is reduced nearly threefold in the normal cell but not in the transformed cell following Ca^2+^ deprivation. Degradation of the EGF‐receptor complex is also sensitive to Ca^2+^. A twofold reduction in the rate of release of acid‐soluble ^125^I occurs in the normal but not the transformed cell under conditions of lowered medium Ca^2+^. In contrast, 2‐chloro‐10‐3‐aminopropyl phenothiazine (CP), an inhibitor of the Ca^2+^‐dependent regulator protein calmodulin, causes an inhibition of [^125^I]EGF internalization and degradation in both the normal and transformed WI38 cell, and a marked inhibition of [^125^I]EGF binding to the cell surface receptor of the transformed cell but not the normal cell.