Signal Transduction Pathways Can Amplify the Effects of Extracellular Signals

Multiple signal transduction proteins are frequently combined to form a signal transduction pathway, allowing multiple target proteins to be activated (or inhibited) by a single type of cell-surface receptor. Figure 15-7 depicts a typical signal transduction pathway downstream of many G protein–coupled receptors. Here, binding of a hormone triggers a conformational change in the receptor, leading to activation of a G protein by catalyzing the exchange of GTP for GDP. The activated G protein binds to and activates an enzyme that synthesizes a second messenger; this small molecule binds and activates a protein kinase that, in turn, phosphorylates and thus changes the activity of one or more target proteins. One specific example of this multiprotein pathway—the regulation of glycogen metabolism in the liver by the hormone epinephrine—is detailed in Section 15.5, and the molecules involved in that pathway are listed in parentheses in Figure 15-7.

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FIGURE 15-7 A signal transduction pathway involving a G protein, a second messenger, a protein kinase, and several target proteins. The figure depicts a generalized signal transduction pathway; in parentheses are listed the molecules involved in the specific signaling pathway discussed in Section 15-5. Binding of the hormone to its cell-surface receptor 1 triggers activation of a G protein 2 by the receptor functioning as a GEF and causing loss of GDP and binding of GTP. The active G protein binds to and activates an enzyme 3 that synthesizes a second messenger 4, which in turn binds to and activates a protein kinase 5. The kinase, in turn, phosphorylates, and thus changes the activity of, one or more target proteins. These proteins can either be cytosolic proteins 6a that induce changes in cellular function, metabolism, or movement or transcription factors 6b that induce changes in gene expression.

One important advantage of a cascade of proteins in a signal transduction pathway is that it facilitates amplification of an extracellular signal. Activation of a single cell-surface receptor protein can result in an increase of perhaps thousands of cAMP molecules or Ca2+ ions in the cytosol. Each of these molecules, in turn, by activating its target protein kinase or other signal transduction protein, can affect the activity of multiple downstream proteins. In many signal transduction pathways, amplification is necessary because cell-surface receptors are typically low-abundance proteins, present in only a thousand or so copies per cell, while the cellular responses induced by the binding of a relatively small number of hormones to the available receptors often require generation of tens or hundreds of thousands of activated effector molecules per cell. In the case of G protein–coupled hormone receptors, signal amplification is possible in part because a single receptor can activate multiple G proteins during the time a hormone remains bound, each of which in turn activates an effector protein. In Section 15.5, we see how this amplification cascade allows blood levels of epinephrine as low as 10−10 M to stimulate conversion of glycogen to glucose by the liver and release of glucose into the blood, and in Figure 15-30 we will see how this amplification can regulate expression of many genes.

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