It is also true, although much less obvious, that this turnover rate can determine the promptness of the response when an extracellular signal arrives. Consider, for example, two intracellular signaling molecules, X and Y, both of which are normally maintained at a steady-state concentration of 1000 molecules per cell. The cell synthesizes and degrades molecule Y at a rate of 100 molecules per second, with each molecule having an average lifetime of 10 seconds. Molecule X has a turnover rate that is 10 times slower than that of Y: it is both synthesized and degraded at a rate of 10 molecules per second, so that each molecule has an average lifetime in the cell of 100 seconds. If a signal acting on the cell causes a tenfold increase in the synthesis rates of both X and Y with no change in the molecular lifetimes, at the end of 1 second the concentration of Y will have increased by nearly 900 molecules per cell (10 × 100 – 100), while the concentration of X will have increased by only 90 molecules per cell. In fact, after a molecule’s synthesis rate has been either increased or decreased abruptly, the time required for the molecule to shift halfway from its old to its new equilibrium concentration is equal to its half-life—that is, equal to the time that would be required for its concentration to fall by half if all synthesis were stopped (Figure 15–14).
The same principles apply to proteins and small molecules, whether the molecules are in the extracellular space or inside cells. Many intracellular proteins have short half-lives, some surviving for less than 10 minutes. In most cases, these are key regulatory proteins whose concentrations are rapidly controlled in the cell by changes in their rates of synthesis.
As we have seen, many cell responses to extracellular signals depend on the conversion of intracellular signaling proteins from an inactive to an active form, rather than on their synthesis or degradation. Phosphorylation or the binding of GTP, for example, commonly activates signaling proteins. Even in these cases, however, the activation must be rapidly and continuously reversed (by dephosphorylation or GTP hydrolysis to GDP, respectively, in these examples) to make rapid signaling possible. These inactivation processes play a crucial part in determining the magnitude, rapidity, and duration of the response.
Figure 15–13 Slow and rapid responses to an extracellular signal. Certain types of signal-induced cellular responses, such as increased cell growth and division, involve changes in gene expression and the synthesis of new proteins; they therefore occur slowly, often starting an hour or more after the signal is received. Other responses—such as changes in cell movement, secretion, or metabolism— need not involve changes in gene transcription and therefore occur much more quickly, often starting in seconds or minutes; they may involve the rapid phosphorylation of effector proteins in the cytoplasm, for example. Synaptic responses mediated by changes in membrane potential are even quicker and can occur in milliseconds (not shown). Some signaling systems generate both rapid and slow responses as shown here, allowing the cell to respond quickly to a signal while simultaneously initiating a more long-term, persistent response.
minutes after the synthesis rate has minutes after the synthesis rate has been decreased by a factor of 10 been increased by a factor of 10 relative concentration of intracellular molecule
Cells Can Respond Abruptly to a Gradually Increasing Signal