The Ca2+-Calmodulin Complex Mediates Many Cellular Responses to External Signals

The ubiquitous small cytosolic protein calmodulin functions as a multipurpose switch protein that mediates many cellular effects of Ca2+ ions. Binding of Ca2+ to four sites on calmodulin triggers a major conformational change that allows calmodulin to bind to and modulate the activity of many enzymes and other proteins (see Figure 3-33). Because four Ca2+ ions bind to calmodulin in a cooperative fashion, a small change in the level of cytosolic Ca2+ leads to a large change in the level of active calmodulin. One well-studied enzyme activated by the Ca2+-calmodulin complex is myosin light-chain kinase, which regulates the activity of myosin and thus contraction in smooth muscle cells (see Chapter 17). Another is PDE, the enzyme that degrades cAMP to 5′-AMP and terminates its effects (see Figure 15-31). This reaction thus links Ca2+ and cAMP, one of many examples in which two second messenger–mediated pathways interact to fine-tune a cellular response.

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In many cells, the rise in cytosolic Ca2+ that follows receptor signaling via phospholipase C–generated IP3 leads to the activation of specific transcription factors. In some cases, Ca2+-calmodulin activates protein kinases that, in turn, phosphorylate transcription factors, thereby modifying their activity and regulating gene expression. In other cases, Ca2+-calmodulin activates a phosphatase that removes phosphate groups from a transcription factor, thus activating it. An important example of this mechanism involves the T cells of the immune system (see Chapter 23).