Multiple Facets of the Modulation of Growth by cAMP

Abstract

Publisher Summary This chapter describes multiple facets of the modulation of growth by cyclic AMP (cAMP). The successes in elucidating the functions of cell-transforming proteins encoded by various oncogenes and the demonstration of antioncogenes have shed light on the assumption that cancers mostly develop from alterations of growth control mechanisms, normally involved in homeostasis, tissue repair, and development. cAMP is the first identified intracellular second messenger of hormone action. Pharmacological and genetic tools used to manipulate the CAMP-PKA cascade are summarized in the chapter. Forskolin, a plant diterpene, activates vertebrate adenylate cyclase directly and enhances its response to activated GS, thus to the receptors that regulate GS. Inhibitors of cyclic nucleotide phosphodiesterases by inhibiting the catabolism of cAMP also raise cAMP levels. It is found that due to the negative cooperativity of the phosphodiesterase system, these inhibitors are much more efficient in increasing the cAMP response to activators of adenylate cyclase than in increasing basal levels of cAMP.