Ionic Signal Transduction by Growth Factors

Abstract

The cell surface plays a crucial role in the regulation of cell metabolism in general and in the regulation of cell proliferation in particular. Receptor proteins in the plasma membrane receive and transduce growth-stimulatory signals that trigger a cascade of biochemical and physiological changes in the cell. Ultimately, this chain of events culminates in replicative DNA synthesis and cell division. Among the most extensively studied mitogens are the polypeptide hormones epidermal growth factor (EGF) and platelet-derived growth factor (PDGF). Although much has been learned about the interaction of EGF and PDGF with their specific receptors on the cell surface, relatively little is known about the ensuing intracellular signals transmitting the mitogenic response from the plasma membrane to the cell nucleus. In the search for putative mitogenic signals, much attention has been focused on the earliest detectable cellular reactions following the addition of growth factors to appropriate target cells. Immediate consequences of growth factor-receptor interaction include tyrosine-specific protein phosphorylations (Ushiro and Cohen, 1980; Ek et al., 1982; Cooper et al., 1982), breakdown of inositol phospholipids (Sawyer and Cohen, 1981; Habenicht et al., 1981), and increased transport of Na⁺, K⁺, and Ca²⁺ across the plasma membrane (Rozengurt and Heppel, 1975; Moolenaar et al., 1981a, 1982a,b; Sawyer and Cohen, 1981).