Signaling Pathways Begin with the Binding of an Extracellular Molecule to a Receptor
In addition to the Rube Goldberg-Iike sequence of signal pathways, another aspect of the overall “strategy” of cellular information transmission is that signaling pathways almost always begin with the environmental signal molecule binding to a protein molecule specialized for information transfer, called a receptor.
The LDL receptor discussed earlier is involved in the transport of material into cells (see Figure 1-12). However, most other receptors are proteins whose task is to transmit and transduce information to the cell from the extracellular environment. Receptors distinguish among the large number of external signaling molecules (e.g., various hormones, neurotransmitters, growth factors) through the usual protein mechanism of highly specific binding.Three broad classes of receptors, called receptor families, are particularly important in physiological function and are discussed in this chapter and Chapter 2. Two of these families, the G-protein-coupled receptors and the receptor tyrosine kinases, are intrinsic membrane proteins of the plasma membrane. These membrane receptors bind the signal molecule in the extracellular environment, and the signal is then communicated intracellularly through a Rube Goldberg sequence of “differences that make a difference.” The third class of receptors is the nuclear receptor family. These intracellular proteins transduce signals from oily, Iipidic molecules that can easily enter the cell, such as steroid and thyroid hormones, fat molecules in the diet, and derivatives of vitamins A and D. The information transduction pathway of nuclear receptors is simpler than that of the membrane receptors in that nuclear receptors are themselves direct regulators of gene transcription; that is, nuclear receptors are transcription factors. Binding of the signal molecule activates the nuclear receptor so that it is then able to bind directly to specific regions of deoxyribonucleic acid (DNA) and stimulate the binding of ribonucleic acid (RNA) polymerase to, and thus production of, messenger RNA from the particular gene or genes in that region of DNA.