Ji

Relative concentration of ligand

▲ EXPERIMENTAL FIGURE 13-3 The maximal physiological response to many external signals occurs when only a fraction of the receptor molecules are occupied by ligand. In this situation, plots of the extent of ligand binding and of physiological response at different ligand concentrations differ. In the example shown here, 50 percent of the maximal physiological response is induced at a ligand concentration at which only 18 percent of the receptors are occupied. Likewise, 80 percent of the maximal response is induced when the ligand concentration equals the Kd value, at which 50 percent of the receptors are occupied.

Physiological response

Fraction of surface receptors with bound ligand

■ Ligand concentration for 50% physiological response has =1000 surface receptors for erythropoietin, which induces progenitor cells to proliferate and differentiate into red blood cells. Because only 100 of these receptors need to bind ery-thropoietin to induce division of a target cell, the ligand concentration needed to induce 50 percent of the maximal cellular response is proportionally lower than the Kd value for binding. In such cases, a plot of the percentage of maximal binding versus ligand concentration differs from a plot of the percentage of maximal cellular response versus ligand concentration.

Sensitivity of a Cell to External Signals Is Determined by the Number of Surface Receptors

Because the cellular response to a particular signaling molecule depends on the number of receptor-ligand complexes, the fewer receptors present on the surface of a cell, the less sensitive the cell is to that ligand. As a consequence, a higher ligand concentration is necessary to induce the usual physiological response than would be the case if more receptors were present.

To illustrate this important point, let's extend our example of a typical erythroid progenitor cell. The Kd for binding of erythropoietin (Epo) to its receptor is about 10"10 M. As we noted above, only 10 percent of the =1000 cell-surface ery-thropoietin receptors on the surface of a cell must be bound to ligand to induce the maximal cellular response. We can determine the ligand concentration, [L], needed to induce the maximal response by rewriting Equation 13-2 as follows:

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