Chapter 8 The Generation of Ionic Signals by Growth Factors

Publisher Summary Polypeptide growth factors play a vital role in the regulation of cell proliferation and development. Several of these factors have been isolated and purified to homogeneity from various biological sources. This chapter focuses on the generation of ionic signals by growth factors, with particular emphasis on the activation of Na+–H+ exchange and the mobilization of Ca2+. Some approaches to assess the interrelationship among the various signal pathways have been described, especially the use of tumor-promoting phorbol esters and of monoclonal antibodies against the human epidermal growth factor (EGF) receptor. The ionic signals in growth factor action include (1) the activation of Na+–H+ exchange, (2) Ca2+ mobilization by growth factors, and (3) the role of inositol lipid breakdown and protein kinase C. Numerous cellular functions are regulated by changes in cytoplasmic free Ca2+ and many of them through the formation of Ca2+ calmodulin complexes. With respect to mitogen action, a rapid rise in Ca2+ seems to be a critical signal for lymphocytes to enter the mitotic cycle. Another powerful tool for the dissociation of molecular events in the mitogenic signal pathway is achieved by the availability of monoclonal antibodies against the EGF receptor.