Compartmentation of Second Messenger Action: Immunocytochemical and Biochemical Evidence

Abstract

Publisher Summary This chapter discusses the compartmentation of second-messenger action. Extensive work has been reported by a number of investigators approaching the problems of compartmentalized second-messenger action. They have produced a body of evidence strongly suggesting that compartmentalization plays a vital role in cellular regulation. Immunocytochemical localization of second messengers and the proteins controlled by cyclic AMP (cAMP), cGMP, and Ca2+ often show distinct subcellular patterns best explained by compartmentation. cAMP serves as the second messenger for numerous hormones, including many catecholamines, prostaglandins, and peptide hormones. cAMP is synthesized intracellularly from ATP by the membrane-associated enzyme complex adenylate cyclase. Hormone binding to a receptor signals the catalytic unit of adenylate cyclase to increase cAMP synthesis rate via an intermediate protein G8. The only known mechanism by which cAMP regulates eukaryotic cellular function is through the activation of cAMP-dependent protein kinases (cA-PKs), of which two general isozymic types exist. The holoenzyme is a tetramer consisting of two catalytic and two regulatory subunits. Kinase activity is regulated by cAMP binding to two sites on each of the regulatory (R) subunits of the cA-PK holoenzyme.