9 - Signal Transduction

Abstract

This chapter discusses signal transduction, whereby an external chemical signal elicits an intracellular metabolic change. The chapter discusses two mechanisms of signal transduction—the generation of second messengers and receptor phosphorylation. The second messengers includes several topics, such as G proteins, cyclic AMP as a second messenger, cyclic GMP as a second messenger, calcium as a second messenger, and second messengers generated by lipid hydrolysis. The chapter also discusses signaling by receptor phosphorylation, two-component systems, and protein tyrosine phosphatase signaling. The process begins with the binding of specific ligands to receptors located at the surface of the plasma membrane. Most signaling appears to involve receptor activation of a GTP-binding protein (G protein). The activated G proteins interact with enzymes that produce second messenger molecules. Changes in cellular enzyme activities lead directly to a physiological response by the cell. Another signaling pathway regulated by the action of G proteins is the cyclic AMP-dependent protein kinase (PKA) pathway. In this pathway, binding of an agonist to a receptor leads to the activation of adenylate cyclase and thus, the production of cAME. Cyclic AMP is a second messenger that activates PKA. PKA catalyzes adenosine triphosphate (ATP) -dependent phosphorylation of cell-specific target proteins. It is the change in activity of the target proteins that ultimately leads to the physiological response of cells bound to an agonist. A second mechanism of signal transduction involves cell surface receptors that have tyrosine kinase activities associated with their cytoplasmic domains. Binding of agonist to these receptors directly activates their kinase domains. The kinase activity catalyzes the phosphorylation of intracellular proteins and often causes autophosphorylation. This phosphorylation may directly cause changes in enzyme activity or may indirectly affect activity by first promoting binding of proteins to the receptor. Binding of extracellular signals to their receptors can result in the modulation of ion channels. In these cases, ions act as second messengers. This process is the least understood mechanism of signal transduction.