Experimental Approaches for Building a Comprehensive View of Signal-Induced Responses
■ About one-third of the genes in humans, flies (Drosophila), and roundworms (C. elegans) are unique to each animal.
■ The presence and distribution of specific mRNAs and proteins can be detected in living cells by in situ hybridization and immunohistochemical staining.
■ DNA microarray analysis allows the full complement of genes to be examined for transcriptional changes that occur in response to environmental changes or extracellular signals and in development (see Figure 15-5).
■ Protein microarrays are proving useful in detecting and monitoring changes in protein-protein associations (see Figure 15-4).
■ The function of a gene found to be activated under certain conditions can be tested by inactivating it and observing the resulting phenotype.
■ Signals, altered environmental conditions, or infection generally evoke not a single response by cells but multiple changes in the pattern of gene transcription, protein modifications, and associations between proteins. By monitoring the totality of these individual responses, researchers are developing comprehensive views of how and why cells respond.
15.2| Responses of Cells to Environmental Influences
Much of this chapter deals with signaling pathways that control how cells change in the course of development. The mature cells of some tissues (e.g., blood and skin) have a relatively short life span compared with that of other types of cells and are constantly being replaced by the differentiation and proliferation of stem cells (Chapter 22). In a sense, such tissues never stop developing. The mature cells of other tissues, such as the brain, are long lived; after such tissues reach maturation, there is little additional differentiation. Mature cells in all tissues, however, are changing constantly in response to metabolic or behavioral demands as well as to injury or infection. In this section, we consider several ways that cells respond to variations in the demand for two environmental inputs—glucose and oxygen—or in their levels.
Integration of Multiple Second Messengers Regulates Glycogenolysis
One way for cells to respond appropriately to current physiological conditions is to sense and integrate more than one signal. A good example comes from glycogenolysis, the hydrolysis of glycogen to yield glucose 1-phosphate. In Chapter 13, we saw that a rise in cAMP induced by epinephrine stimulation of ^-adrenergic receptors promotes glycogen breakdown in muscle and liver cells (see Figure 13-17). In both muscle and liver cells, other second messengers also produce the same cellular response.
In muscle cells, stimulation by nerve impulses causes the release of Ca2+ ions from the sarcoplasmic reticulum and an increase in the cytosolic Ca2+ concentration, which triggers muscle contraction. The rise in cytosolic Ca2+ also activates glycogen phosphorylase kinase (GPK), thereby stimulating the degradation of glycogen to glucose 1-phosphate, which fuels prolonged contraction. Recall that phosphorylation by cAMP-dependent protein kinase A also activates glycogen phosphorylase kinase. Thus this key regulatory enzyme in glycogenolysis is subject to both neural and hormonal regulation in muscle (Figure 15-6a).
(a) Muscle cells
(b) Liver cells
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