Activation of the enzyme sets off a chain of events within the cell that eventually leads to a response. One example of this type of enzyme-linked receptor is the tyrosine kinase receptor Figure 9.
A kinase is an enzyme that transfers phosphate groups from ATP to another protein. The tyrosine kinase receptor transfers phosphate groups to tyrosine molecules tyrosine residues. First, signaling molecules bind to the extracellular domain of two nearby tyrosine kinase receptors.
The two neighboring receptors then bond together, or dimerize. Phosphates are then added to tyrosine residues on the intracellular domain of the receptors phosphorylation. The phosphorylated residues can then transmit the signal to the next messenger within the cytoplasm. A receptor tyrosine kinase is an enzyme-linked receptor with a single transmembrane region and extracellular and intracellular domains. Binding of a signaling molecule to the extracellular domain causes the receptor to dimerize.
Tyrosine residues on the intracellular domain are then autophosphorylated, triggering a downstream cellular response. The signal is terminated by a phosphatase that removes the phosphates from the phosphotyrosine residues. Produced by signaling cells and the subsequent binding to receptors in target cells, ligands act as chemical signals that travel to the target cells to coordinate responses.
Small hydrophobic ligands can directly diffuse through the plasma membrane and interact with internal receptors. Important members of this class of ligands are the steroid hormones. Steroids are lipids that have a hydrocarbon skeleton with four fused rings; different steroids have different functional groups attached to the carbon skeleton.
Steroid hormones include the female sex hormone, estradiol, which is a type of estrogen; the male sex hormone, testosterone; and cholesterol, which is an important structural component of biological membranes and a precursor of steroid hormones Figure 9. Other hydrophobic hormones include thyroid hormones and vitamin D.
In order to be soluble in blood, hydrophobic ligands must bind to carrier proteins while they are being transported through the bloodstream. Steroid hormones have similar chemical structures to their precursor, cholesterol. Because these molecules are small and hydrophobic, they can diffuse directly across the plasma membrane into the cell, where they interact with internal receptors. Water-soluble ligands are polar and therefore cannot pass through the plasma membrane unaided; sometimes, they are too large to pass through the membrane at all.
Instead, most water-soluble ligands bind to the extracellular domain of cell-surface receptors. This group of ligands is quite diverse and includes small molecules, peptides, and proteins. Nitric oxide NO is a gas that also acts as a ligand. It is able to diffuse directly across the plasma membrane, and one of its roles is to interact with receptors in smooth muscle and induce relaxation of the tissue. NO has a very short half-life and therefore only functions over short distances.
Nitroglycerin, a treatment for heart disease, acts by triggering the release of NO, which causes blood vessels to dilate expand , thus restoring blood flow to the heart. NO has become better known recently because the pathway that it affects is targeted by prescription medications for erectile dysfunction, such as Viagra erection involves dilated blood vessels. Hormones mediate changes in target cells by binding to specific hormone receptors. In this way, even though hormones circulate throughout the body and come into contact with many different cell types, they only affect cells that possess the necessary receptors.
Receptors for a specific hormone may be found on many different cells or may be limited to a small number of specialized cells. For example, thyroid hormones act on many different tissue types, stimulating metabolic activity throughout the body. Cells can have many receptors for the same hormone but often also possess receptors for different types of hormones. Additionally, the number of receptors that respond to a hormone can change over time, resulting in increased or decreased cell sensitivity.
In up-regulation , the number of receptors increases in response to rising hormone levels, making the cell more sensitive to the hormone and allowing for more cellular activity. When the number of receptors decreases in response to rising hormone levels, called down-regulation , cellular activity is reduced. Receptor binding alters the cellular activity and results in an increase or decrease in normal body processes.
Depending on the location of the protein receptor on the target cell and the chemical structure of the hormone, hormones can mediate changes directly by binding to intracellular hormone receptors and modulating gene transcription, or indirectly by binding to cell surface receptors and stimulating signaling pathways. Lipid-derived soluble hormones such as steroid hormones diffuse across the membranes of the endocrine cell. Once outside the cell, they bind to transport proteins that keep them soluble in the bloodstream.
At the target cell, the hormones are released from the carrier protein and diffuse across the lipid bilayer of the plasma membrane of cells. The steroid hormones pass through the plasma membrane of a target cell and adhere to intracellular receptors residing in the cytoplasm or in the nucleus. The hormones and receptor complex act as transcription regulators by increasing or decreasing the synthesis of mRNA molecules of specific genes.
This, in turn, determines the amount of corresponding protein that is synthesized by altering gene expression. This protein can be used either to change the structure of the cell or to produce enzymes that catalyze chemical reactions. Receptors are generally transmembrane proteins, which bind to signaling molecules outside the cell and subsequently transmit the signal through a sequence of molecular switches to internal signaling pathways. Membrane receptors fall into three major classes: G-protein-coupled receptors, ion channel receptors, and enzyme-linked receptors.
The names of these receptor classes refer to the mechanism by which the receptors transform external signals into internal ones — via protein action, ion channel opening, or enzyme activation, respectively. Because membrane receptors interact with both extracellular signals and molecules within the cell, they permit signaling molecules to affect cell function without actually entering the cell.
This is important because most signaling molecules are either too big or too charged to cross a cell's plasma membrane Figure 1. Not all receptors exist on the exterior of the cell.
Some exist deep inside the cell, or even in the nucleus. These receptors typically bind to molecules that can pass through the plasma membrane, such as gases like nitrous oxide and steroid hormones like estrogen. Figure 1: An example of ion channel activation An acetylcholine receptor green forms a gated ion channel in the plasma membrane.
This receptor is a membrane protein with an aqueous pore, meaning it allows soluble materials to travel across the plasma membrane when open. When no external signal is present, the pore is closed center. When acetylcholine molecules blue bind to the receptor, this triggers a conformational change that opens the aqueous pore and allows ions red to flow into the cell. Once a receptor protein receives a signal, it undergoes a conformational change, which in turn launches a series of biochemical reactions within the cell.
These intracellular signaling pathways, also called signal transduction cascades , typically amplify the message, producing multiple intracellular signals for every one receptor that is bound. Activation of receptors can trigger the synthesis of small molecules called second messengers , which initiate and coordinate intracellular signaling pathways.
In fact, it was the first second messenger ever discovered. The activation of adenylyl cyclase can result in the manufacture of hundreds or even thousands of cAMP molecules. These cAMP molecules activate the enzyme protein kinase A PKA , which then phosphorylates multiple protein substrates by attaching phosphate groups to them. Each step in the cascade further amplifies the initial signal, and the phosphorylation reactions mediate both short- and long-term responses in the cell Figure 2.
How does cAMP stop signaling? It is degraded by the enzyme phosphodiesterase. Other examples of second messengers include diacylglycerol DAG and inositol 1,4,5-triphosphate IP3 , which are both produced by the enzyme phospholipase , also a membrane protein. Figure 2: An example of a signal transduction cascade involving cyclic AMP The binding of adrenaline to an adrenergic receptor initiates a cascade of reactions inside the cell. The signal transduction cascade begins when adenylyl cyclase, a membrane- bound enzyme, is activated by G-protein molecules associated with the adrenergic receptor.
Enzymes in the synaptic cleft degrade some types of neurotransmitters to terminate the signal. Signals that act locally between cells that are close together are called paracrine signals. Paracrine signals move by diffusion through the extracellular matrix.
These types of signals usually elicit quick responses that last only a short amount of time. In order to keep the response localized, paracrine ligand molecules are normally quickly degraded by enzymes or removed by neighboring cells. Removing the signals will reestablish the concentration gradient for the signal, allowing them to quickly diffuse through the intracellular space if released again.
One example of paracrine signaling is the transfer of signals across synapses between nerve cells. A nerve cell consists of a cell body, several short, branched extensions called dendrites that receive stimuli, and a long extension called an axon, which transmits signals to other nerve cells or muscle cells.
The junction between nerve cells where signal transmission occurs is called a synapse. A synaptic signal is a chemical signal that travels between nerve cells.
Signals within the nerve cells are propagated by fast-moving electrical impulses. When these impulses reach the end of the axon, the signal continues on to a dendrite of the next cell by the release of chemical ligands called neurotransmitters by the presynaptic cell the cell emitting the signal.
The neurotransmitters are transported across the very small distances between nerve cells, which are called chemical synapses Figure 2. The tyrosine kinase receptor transfers phosphate groups to tyrosine molecules. Signaling molecules bind to the extracellular domain of two nearby tyrosine kinase receptors, which then dimerize.
Phosphates are then added to tyrosine residues on the intracellular domain of the receptors and can then transmit the signal to the next messenger within the cytoplasm.
Signaling molecules are necessary for the coordination of cellular responses by serving as ligands and binding to cell receptors. Compare and contrast the different types of signaling molecules: hydrophobic, water-soluble, and gas ligands.
Produced by signaling cells and the subsequent binding to receptors in target cells, ligands act as chemical signals that travel to the target cells to coordinate responses. Small hydrophobic ligands can directly diffuse through the plasma membrane and interact with internal receptors.
Important members of this class of ligands are the steroid hormones. Steroids are lipids that have a hydrocarbon skeleton with four fused rings; different steroids have different functional groups attached to the carbon skeleton. Steroid hormones include the female sex hormone, estradiol, which is a type of estrogen; the male sex hormone, testosterone; and cholesterol, which is an important structural component of biological membranes and a precursor of steriod hormones.
Other hydrophobic hormones include thyroid hormones and vitamin D. In order to be soluble in blood, hydrophobic ligands must bind to carrier proteins while they are being transported through the bloodstream.
Steroid Hormones : Steroid hormones have similar chemical structures to their precursor, cholesterol. Because these molecules are small and hydrophobic, they can diffuse directly across the plasma membrane into the cell, where they interact with internal receptors.
Water-soluble ligands are polar and, therefore, cannot pass through the plasma membrane unaided; sometimes, they are too large to pass through the membrane at all. Instead, most water-soluble ligands bind to the extracellular domain of cell-surface receptors. Cell-surface receptors include: ion-channel, G-protein, and enzyme-linked protein receptors.
The binding of these ligands to these receptors results in a series of cellular changes. These water soluble ligands are quite diverse and include small molecules, peptides, and proteins.
Nitric oxide NO is a gas that also acts as a ligand. It is able to diffuse directly across the plasma membrane; one of its roles is to interact with receptors in smooth muscle and induce relaxation of the tissue.
NO has a very short half-life; therefore, it only functions over short distances. Nitroglycerin, a treatment for heart disease, acts by triggering the release of NO, which causes blood vessels to dilate expand , thus restoring blood flow to the heart.
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Signaling Molecules and Cellular Receptors Cellular communication ensures regulation of biological processes within various environments from single-celled to multicellular organisms. Learning Objectives Explain the importance of cell communication. Key Takeaways Key Points The ability of cells to communicate through chemical signals originated in single cells and was essential for the evolution of multicellular organisms. Cells can receive a message, transfer the information across the plasma membrane, and then produce changes within the cell in response to the message.
Single-celled organisms, like yeast and bacteria, communicate with each other to aid in mating and coordination. Cellular communication has developed as a means to communicate with the environment, produce biological changes, and, if necessary, ensure survival.
Key Terms biofilm : a thin film of mucus created by and containing a colony of bacteria and other microorganisms. Forms of Signaling The major types of signaling mechanisms that occur in multicellular organisms are paracrine, endocrine, autocrine, and direct signaling. Learning Objectives Describe four types of signaling found in multicellular organisms. Key Takeaways Key Points Cells communicate via various types of signaling that allow chemicals to travel to target sites in order to elicit a response.
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