Chapter 12 BIOCHEMICAL SIGNALING
The ability of cells to receive and act on signals from outside the plasma membrane is fundamental to life. Cells and organisms constantly sample the surrounding medium for nutrients, oxygen, light, and sexual partners, and for the presence of noxious chemicals, predators, or competitors for food. These signals elicit appropriate responses, such as motion toward food or away from toxic substances. In multicellular organisms, cells exchange hundreds of signals — neurotransmitters, hormones, key metabolites — which trigger appropriate responses in such cellular activities as metabolism, cell division, embryonic growth and development, movement, and defense. In all these cases, the signal represents information that is detected by specific receptors and converted to a cellular response, which always involves a chemical process. This conversion of information into a chemical change, signal transduction, is a universal property of living cells.
In this chapter, we present examples of specific biological signaling systems from which we have acquired our current understanding of the biochemistry of signal transduction in animals. We emphasize the following principles:
Cells respond to external signals through receptor-mediated processes that amplify the signal, integrate it with input from other receptors, transmit the signal to the appropriate effectors, and eventually end the response.
There is a high degree of evolutionary conservation of signaling proteins and transduction mechanisms across the animal phyla. At least a billion years of evolution have passed since the plant and animal branches of the eukaryotes diverged, which is reflected in the differences in signaling mechanisms used in the two kingdoms. We focus here on the animal kingdom.
In multicellular animals, GPCRs with seven transmembrane helices are the largest group of plasma membrane receptors. These G Protein–Coupled Receptors act through G proteins, which are turned on when they bind guanosine triphosphate (GTP). Animals have hundreds of different GPCRs, each able to respond to a specific signal.
Plasma membrane receptors with an intracellular tyrosine kinase activity act through cascades of protein kinases to transduce signals about the metabolic state, including growth factors.
Phosphorylation of intrinsically disordered regions of signaling proteins acts as a switch, toggling enzyme activity, or creating binding sites for other molecules. Signal responses are integrated by multiprotein signaling complexes with modular domains that bind phosphorylated Tyr, Ser, or Thr residues.
Ion channels gated by membrane potential or ligands are central to signaling in all cells, including bacteria, plants, and animals.
Some hormone signals act inside the cell, not at the plasma membrane, forming complexes with specific receptor proteins that regulate gene expression.
Cells receive extracellular signals that determine progress through the cell division cycle, or trigger cell death — processes regulated by phosphorylation and dephosphorylation of key regulatory proteins.
Defective signaling proteins or defective regulation of their synthesis and breakdown can disrupt cell cycle regulation and lead to tumor formation (cancer).
Cells respond to external signals through receptor-mediated processes that amplify the signal, integrate it with input from other receptors, transmit the signal to the appropriate effectors, and eventually end the response.
There is a high degree of evolutionary conservation of signaling proteins and transduction mechanisms across the animal phyla. At least a billion years of evolution have passed since the plant and animal branches of the eukaryotes diverged, which is reflected in the differences in signaling mechanisms used in the two kingdoms. We focus here on the animal kingdom.
In multicellular animals, GPCRs with seven transmembrane helices are the largest group of plasma membrane receptors. These G Protein–Coupled Receptors act through G proteins, which are turned on when they bind guanosine triphosphate (GTP). Animals have hundreds of different GPCRs, each able to respond to a specific signal.
Plasma membrane receptors with an intracellular tyrosine kinase activity act through cascades of protein kinases to transduce signals about the metabolic state, including growth factors.
Phosphorylation of intrinsically disordered regions of signaling proteins acts as a switch, toggling enzyme activity, or creating binding sites for other molecules. Signal responses are integrated by multiprotein signaling complexes with modular domains that bind phosphorylated Tyr, Ser, or Thr residues.
Ion channels gated by membrane potential or ligands are central to signaling in all cells, including bacteria, plants, and animals.
Some hormone signals act inside the cell, not at the plasma membrane, forming complexes with specific receptor proteins that regulate gene expression.
Cells receive extracellular signals that determine progress through the cell division cycle, or trigger cell death — processes regulated by phosphorylation and dephosphorylation of key regulatory proteins.
Defective signaling proteins or defective regulation of their synthesis and breakdown can disrupt cell cycle regulation and lead to tumor formation (cancer).