Signaling Molecules and Cell-Surface Receptors
■ Extracellular signaling molecules regulate interactions between unicellular organisms and are critical regulators of physiology and development in multicellular organisms.
■ Binding of extracellular signaling molecules to cell-surface receptors triggers intracellular signal-transduction pathways that ultimately modulate cellular metabolism, function, or gene expression (Figure 13-1).
■ External signals include membrane-anchored and secreted proteins and peptides, small lipophilic molecules (e.g., steroid hormones, thyroxine), small hydrophilic mol
Receptor for ligand other than X
ecules derived from amino acids (e.g., epinephrine), gases (e.g., nitric oxide), and physical stimuli (e.g., light).
■ Signals from one cell can act on nearby cells (paracrine), on distant cells (endocrine), or on the signaling cell itself (autocrine).
■ Receptors bind ligands with considerable specificity, which is determined by noncovalent interactions between a ligand and specific amino acids in the receptor protein (see Figure 13-2).
■ The maximal response of a cell to a particular ligand generally occurs at ligand concentrations at which most of its receptors are still not occupied (see Figure 13-3).
■ The concentration of ligand at which half its receptors are occupied, the Kd, can be determined experimentally and is a measure of the affinity of the receptor for the ligand (see Figure 13-4).
■ Because the amount of a particular receptor expressed is generally quite low (ranging from «2000 to 20,000 molecules per cell), biochemical purification may not be feasible. Genes encoding low-abundance receptors for specific ligands often can be isolated from cDNA libraries trans-fected into cultured cells.
■ Functional expression assays can determine if a cDNA encodes a particular receptor and are useful in studying the effects on receptor function of specific mutations in its sequence (see Figure 13-6).
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