Receptors come in two flavors: cell surface and intracellular. Cell surface receptors respond to ligand binding by sending signals into the cell or changing ion permeabililty. On the other hand, ligand binding to an intracellular receptor alters gene expression (the proteins produced by the cell). Intracellular receptors are called nuclear receptors because they act on genes in the nucleus. The actions that take place within the cell in response to receptor binding is signal transduction.
The first figure shows an example of one of the many possible signal transduction pathways that result from ligand binding to a cell surface receptor. Large and soluble ligands bind to receptors on the membrane surface. Exaamples include insulin and glucagon. These ligands do not enter the cell. When they bind to the receptor, a cascade of reactions begins. In most cases, this signal transduction involves second messenger molecules that alter cellular function. (The first messenger is the ligand binding to the cell membrane receptor, but it is never called that.)
In this particular example, a water-soluble hormone (1) binds to a cell surface receptor. The binding (2) activates a G-protein that is coupled to the receptor. Such receptors are called G-protein coupled receptors (GPCRs) and are the most common biological target of drugs. The activated G protein (3) activates the intracellular enzyme adenylyl cyclase, which (4) converts ATP to cAMP, the second messenger. cAMP (5) activates protein kinases which (6) phosphorylate critical regulatory proteins in the cell. Phosphorylation activates some proteins and inhibits others. This shifts the cell into a different functional state.
The second figure shows a typical lipid-soluble ligand binding to an intracellular receptor. Examples include steroid hormones and thyroid hormones. Hormone binding to the receptor alters the proteins that are produced by the cell, by acting on the DNA transcription apparatus that makes mRNA that codes for protein. That is, gene expression is changed by the binding of the hormone to its receptor. For this reason, intracellular receptors are usually called nuclear hormone receptors.
In this example, a lipid-soluble hormone, which is carried in the blood bound to a transporter, is (1) released from the transporter so that it may enter the interstitial fluids bathing a target cell. The hormone (2) passes directly through the cell membrane to enter the cell. Once inside the cell, the hormone (3) binds to an intracellular receptor, forming a receptor-hormone complex. The hormone-receptor complex enters the cell and (4) triggers a change in gene expression, by binding to control elements on the DNA. The transcribed mRNA leaves the nucleus to (5) enter the cytoplasm where it produces a protein that alters cellular function.
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