9: Cell Communication

Question 1

What is an autocrine signal?

Answer 1

A signal that is sent and received by the same or similar nearby cells.

Question 2

What is a cell-surface receptor?

Answer 2

A cell-surface protein that transmits a signal from the exterior of the cell to the interior, even though the ligand does not enter the cell. AKA transmembrane receptor.

Question 3

What is a chemical synapse?

Answer 3

A small space between axon terminals and dendrites of nerve cells where neurotransmitters function.

Question 4

What is an endocrine cell?

Answer 4

A cell that releases ligands involved in endocrine signaling (hormones).

Question 5

What is an endocrine signal?

Answer 5

A long-distance signal that is delivered by ligands (hormones) traveling through an organism’s circulatory system from the signaling cell to the target cell.

Question 6

What is an enzyme-linked receptor?

Answer 6

A cell-surface receptor with intracellular domains that are associated with membrane-bound enzymes.

Question 7

What is an extracellular domain?

Answer 7

A region of a cell-surface receptor that is located on the cell surface.

Question 8

What is a G-protein-linked receptor?

Answer 8

A cell-surface receptor that activates membrane-bound G-proteins to transmit a signal from the receptor to nearby membrane components.

Question 9

What is intercellular signaling?

Answer 9

Communication between cells.

Question 10

What is an internal receptor?

Answer 10

A receptor protein that is located in the cytosol of a cell and binds to ligands that pass through the plasma membrane. AKA intracellular receptor.

Question 11

What is an intracellular mediator?

Answer 11

A small molecule that transmits signals within a cell. AKA second messenger.

Question 12

What is intracellular signaling?

Answer 12

Communication within cells.

Question 13

What is an ion channel-linked receptor?

Answer 13

A cell-surface receptor that forms a plasma membrane channel, which opens when a ligand binds to the extracellular domain (ligand-gated channels).

Question 14

What is a ligand?

Answer 14

A molecule produced by a signaling cell that binds with a specific receptor, delivering a signal in the process.

Question 15

What is a neurotransmitter?

Answer 15

A chemical ligand that carries a signal from one nerve cell to the next.

Question 16

What is a paracrine signal?

Answer 16

A signal between nearby cells that is delivered by ligands traveling in the liquid medium in the space between the cells.

Question 17

What is a receptor?

Answer 17

A protein in or on a target cell that binds to ligands.

Question 18

What is a signaling cell?

Answer 18

A cell that releases signal molecules that allow communication with another cell.

Question 19

What is a synaptic signal?

Answer 19

A chemical signal (neurotransmitter) that travels between nerve cells.

Question 20

What is a target cell?

Answer 20

A cell that has a receptor for a signal or ligand from a signaling cell.

Question 21

What is the specificity of ligands and receptors?

Answer 21

Ligands and receptors exist in several varieties; however, a specific ligand will have a specific receptor that typically binds only that ligand.

Question 22

What are the categories of chemical signaling found in multicellular organisms?

Answer 22

There are four categories: paracrine signaling, endocrine signaling, autocrine signaling, and direct signaling across gap junctions. The main difference between the different categories of signaling is the distance that the signal travels through the organism to reach the target cell. Not all cells are affected by the same signals.

Question 23

How are paracrine signals propagated?

Answer 23

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.

Question 24

What is an example of paracrine signaling?

Answer 24

One example of paracrine signaling is the transfer of signals across synapses between nerve cells.

Question 25

What is a nerve cell?

Answer 25

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.

Question 26

How how are signals in nerve cells propagated?

Answer 26

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. When the neurotransmitter binds the receptor on the surface of the postsynaptic cell, the electrochemical potential of the target cell changes, and the next electrical impulse is launched. The neurotransmitters that are released into the chemical synapse are degraded quickly or get reabsorbed by the presynaptic cell so that the recipient nerve cell can recover quickly and be prepared to respond rapidly to the next synaptic signal.

Question 27

Where are endocrine cells found?

Answer 27

In the body, many endocrine cells are located in endocrine glands, such as the thyroid gland, the hypothalamus, and the pituitary gland.

Question 28

What is the effect of endocrine signals?

Answer 28

Endocrine signals usually produce a slower response but have a longer-lasting effect.

Question 29

What is a hormone?

Answer 29

The ligands released in endocrine signaling are called hormones, signaling molecules that are produced in one part of the body but affect other body regions some distance away.

Question 30

How do hormones move through the body?

Answer 30

Hormones travel the large distances between endocrine cells and their target cells via the bloodstream, which is a relatively slow way to move throughout the body. Because of their form of transport, hormones get diluted and are present in low concentrations when they act on their target cells. This is different from paracrine signaling, in which local concentrations of ligands can be very high.

Question 31

What is the target of autocrine signals?

Answer 31

Autocrine signals are produced by signaling cells that can also bind to the ligand that is released. This means the signaling cell and the target cell can be the same or a similar cell.

Question 32

What are some examples of autocrine signaling?

Answer 32

Autocrine signaling often occurs during the early development of an organism to ensure that cells develop into the correct tissues and take on the proper function. Autocrine signaling also regulates pain sensation and inflammatory responses. Further, if a cell is infected with a virus, the cell can signal itself to undergo programmed cell death, killing the virus in the process.

Question 33

What is an example of autocrine signals targeting neighbor cells?

Answer 33

In some cases, neighboring cells of the same type are also influenced by the released ligand. In embryological development, this process of stimulating a group of neighboring cells may help to direct the differentiation of identical cells into the same cell type, thus ensuring the proper developmental outcome.

Question 34

How are gap junctions used for cell signaling?

Answer 34

Gap junctions in animals and plasmodesmata in plants are connections between the plasma membranes of neighboring cells. These water-filled channels allow small signaling molecules, called intracellular mediators, to diffuse between the two cells. Small molecules, such as calcium ions (Ca²⁺), are able to move between cells, but large molecules like proteins and DNA cannot fit through the channels. The specificity of the channels ensures that the cells remain independent but can quickly and easily transmit signals. The transfer of signaling molecules communicates the current state of the cell that is directly next to the target cell; this allows a group of cells to coordinate their response to a signal that only one of them may have received. In plants, plasmodesmata are ubiquitous, making the entire plant into a giant, communication network.

Question 35

What are the types of receptors?

Answer 35

There are two types of receptors, internal receptors and cell-surface receptors.

Question 36

What is gene expression?

Answer 36

Gene expression is the cellular process of transforming the information in a cell’s DNA into a sequence of amino acids.

Question 37

How can internal signals be used to moderate gene expression?

Answer 37

When a ligand binds to an internal receptor, a conformational change is triggered that exposes a DNA-binding site on the protein. The ligand-receptor complex moves into the nucleus, and binds to specific regulatory regions of the chromosomal DNA and promotes the initiation of transcription. Internal receptors can directly influence gene expression without having to pass the signal on to other receptors or messengers.

Question 38

What do cell-surface receptors do?

Answer 38

A cell-surface receptor spans the plasma membrane and performs signal transduction, in which an extracellular signal is converted into an intercellular signal. Ligands that interact with cell-surface receptors do not have to enter the cell that they affect. Cell-surface receptors are also called cell-specific proteins or markers because they are specific to individual cell types.

Question 39

What are some risks of cell-surface receptor failure?

Answer 39

Because cell-surface receptor proteins are fundamental to normal cell functioning, malfunctions in any one of these proteins could have severe consequences. Errors in the protein structures of certain receptor molecules have been shown to play a role in hypertension (high blood pressure), asthma, heart disease, and cancer.

Question 40

How are cell-surface receptors structured?

Answer 40

Each cell-surface receptor has three main components: an external ligand-binding domain, a hydrophobic membrane-spanning region, and an intracellular domain inside the cell. The ligand-binding domain is also called the extracellular domain. The size and extent of each of these domains vary widely, depending on the type of receptor.

Question 41

How do viruses survive and reproduce?

Answer 41

Unlike living cells, many viruses do not have a plasma membrane or any of the structures necessary to sustain life. Some viruses are simply composed of an inert protein shell containing DNA or RNA. To reproduce, viruses must invade a living cell, which serves as a host, and then take over the hosts cellular apparatus.

Question 42

How does a virus recognize its host?

Answer 42

Viruses often bind to cell-surface receptors on the host cell. Chemical differences in the cell-surface receptors among hosts mean that a virus that infects a specific species cannot infect another species.

Question 43

Which receptors does the flu virus bind to?

Answer 43

The virus that causes human influenza (flu) binds specifically to receptors on membranes of cells of the respiratory system.

Question 44

How do viruses spread between species?

Answer 44

Viruses have very small amounts of DNA or RNA, and, as a result, viral reproduction can occur rapidly. Viral reproduction invariably produces errors that can lead to changes in newly produced viruses; these changes mean that the viral proteins that interact with cell-surface receptors may evolve in such a way that they can bind to receptors in a new host. Such changes happen randomly and quite often in the reproductive cycle of a virus, but the changes only matter if a virus with new binding properties comes into contact with a suitable host. Once a virus jumps to a new host, it can spread quickly.

Question 45

Where do flu viruses originate?

Answer 45

In the case of influenza, the virus can spread to humans in settings where animals and people are in close contact, such as poultry and swine farms.

Question 46

Why is it important to monitor emerging viruses?

Answer 46

Scientists watch newly appearing viruses (called emerging viruses) closely in the hope that such monitoring can reduce the likelihood of global viral epidemics.

Question 47

What are the categories of cell-surface receptors?

Answer 47

There are three general categories of cell-surface receptors: ion channel-linked receptors, G-protein-linked receptors, and enzyme-linked receptors.

Question 48

How do ion channel-linked receptors work?

Answer 48

To form a channel, this type of cell-surface receptor has an extensive membrane-spanning region. In order to interact with the phospholipid fatty acid tails that form the center of the plasma membrane, many of the amino acids in the membrane-spanning region are hydrophobic in nature. Conversely, the amino acids that line the inside of the channel are hydrophilic to allow for the passage of water or ions. When a ligand binds to the extracellular region of the channel, there is a conformational change in the proteins structure that allows ions such as sodium, calcium, magnesium, and hydrogen to pass through.

Question 49

How are G-protein-linked receptors activated?

Answer 49

G-protein-linked receptors bind a ligand and activate a membrane protein called a G-protein. The activated G-protein then interacts with either an ion channel or an enzyme in the membrane. All G-protein-linked receptors have seven transmembrane domains, but each receptor has its own specific extracellular domain and G-protein-binding site.

Question 50

How do G-protein-linked receptors work?

Answer 50

Cell signaling using G-protein-linked receptors occurs as a cyclic series of events. Before the ligand binds, the inactive G-protein can bind to a newly revealed site on the receptor specific for its binding. Once the G-protein binds to the receptor, the resultant shape change activates the G-protein, which releases GDP and picks up GTP. The subunits of the G-protein then split into the α subunit and the βγ subunit. One or both of these G-protein fragments may be able to activate other proteins as a result. After awhile, the GTP on the active α subunit of the G-protein is hydrolyzed to GDP and the βγ subunit is deactivated. The subunits reassociate to form the inactive G-protein and the cycle begins anew.

Question 51

What are some diseases caused by the inhibition of G-protein-linked receptors?

Answer 51

G-protein-linked receptors have been extensively studied and much has been learned about their roles in maintaining health. Bacteria that are pathogenic to humans can release poisons that interrupt specific G-protein-linked receptor function, leading to illnesses such as pertussis, botulism, and cholera.

Question 52

What is the cause and effect of cholera?

Answer 52

In cholera, the water-borne bacterium Vibrio cholerae produces a toxin, choleragen, that binds to cells lining the small intestine. The toxin then enters these intestinal cells, where it modifies a G-protein that controls the opening of a chloride channel and causes it to remain continuously active, resulting in large losses of fluids from the body and potentially fatal dehydration as a result.

Question 53

How is cholera spread?

Answer 53

Transmitted primarily through contaminated drinking water, cholera is a major cause of death in the developing world and in areas where natural disasters interrupt the availability of clean water. Modern sanitation eliminates the threat of cholera outbreaks, such as the one that swept through New York City in 1866.

Question 54

How do enzyme-linked receptors work?

Answer 54

Enzyme-linked receptors are cell-surface receptors with intracellular domains that are associated with an enzyme. In some cases, the intracellular domain of the receptor itself is an enzyme. Other enzyme-linked receptors have a small intracellular domain that interacts directly with an enzyme. The enzyme-linked receptors normally have large extracellular and intracellular domains, but the membrane-spanning region consists of a single alpha-helical region of the peptide strand. When a ligand binds to the extracellular domain, a signal is transferred through the membrane, activating the enzyme. Activation of the enzyme sets off a chain of events within the cell that eventually leads to a response.

Question 55

What is an example of an enzyme-linked receptor?

Answer 55

One example of this type of enzyme-linked receptor is the tyrosine kinase receptor. 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 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.

Question 56

What is an example of the treatment of a malfunctioning enzyme-linked receptor?

Answer 56

HER2 is a receptor tyrosine kinase. In 30 percent of human breast cancers, HER2 is permanently activated, resulting in unregulated cell division. Lapatinib, a drug used to treat breast cancer, inhibits HER2 receptor tyrosine kinase autophosphorylation (the process by which the receptor adds phosphates onto itself), thus reducing tumor growth by 50 percent.

Question 57

What types of molecules can serve as ligands?

Answer 57

The types of molecules that serve as ligands are incredibly varied and range from small proteins to small ions like calcium (Ca²⁺).

Question 58

How do small hydrophobic ligands work?

Answer 58

Small hydrophobic ligands can directly diffuse through the plasma membrane and interact with internal receptors. In order to be soluble in blood, hydrophobic ligands must bind to carrier proteins while they are being transported through the bloodstream.

Question 59

What are steroids?

Answer 59

Steroids are lipids that have a hydrocarbon skeleton with four fused rings; different steroids have different functional groups attached to the carbon skeleton.

Question 60

What are some examples of small hydrophobic ligands?

Answer 60

Important members of this class of ligands are the steroid hormones. 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. Other hydrophobic hormones include thyroid hormones and vitamin D.

Question 61

How do water-soluble ligands work?

Answer 61

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.

Question 62

What is nitric oxide (NO)?

Answer 62

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.

Question 63

What are some medical treatments that trigger the release of NO?

Answer 63

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).

Question 64

What is cyclic AMP (cAMP)?

Answer 64

A second messenger that is derived from ATP.

Question 65

What is cyclic AMP-dependent kinase?

Answer 65

A kinase that is activated by binding to cAMP. AKA protein kinase A, or PKA.

Question 66

What is diacylglycerol (DAG)?

Answer 66

The cleavage product of PIP₂ that is used for signaling within the plasma membrane.

Question 67

What is a dimer?

Answer 67

A chemical compound formed when two molecules join together.

Question 68

What is dimerization of receptor proteins?

Answer 68

The interaction of two receptor proteins to form a functional complex called a dimer.

Question 69

What is an inositol phospholipid?

Answer 69

A lipid present at small concentrations in the plasma membrane that is converted into a second messenger; it has inositol (a carbohydrate) as its hydrophilic head group.

Question 70

What is inositol triphosphate (IP₃)?

Answer 70

The cleavage product of PIP₂ that is used for signaling within the cell.

Question 71

What is a kinase?

Answer 71

An enzyme that catalyzes the transfer of a phosphate group from ATP to another molecule.

Question 72

What is a second messenger?

Answer 72

A small, non-protein molecule that propagates a signal within the cell after activation of a receptor causes its release.

Question 73

What is signal integration?

Answer 73

The interaction of signals from two or more different cell-surface receptors that merge to activate the same response in the cell.

Question 74

What is signal transduction?

Answer 74

Propagation of the signal through the cytoplasm (and sometimes also the nucleus) of the cell.

Question 75

What is a signaling pathway?

Answer 75

Chain of events that occurs in the cytoplasm of the cell to propagate the signal from the plasma membrane to produce a response. AKA signaling cascade.

Question 76

How does ligand binding initiate signal transduction?

Answer 76

When a ligand binds to its receptor, conformational changes occur that affect the receptor’s intracellular domain. Conformational changes of the extracellular domain upon ligand binding can propagate through the membrane region of the receptor and lead to activation of the intracellular domain or its associated proteins. In some cases, binding of the ligand causes dimerization of the receptor. The binding of the receptors in this manner enables their intracellular domains to come into close contact and activate each other.

Question 77

How does ligand binding lead to changes in a cell?

Answer 77

After the ligand binds to the cell-surface receptor, the activation of the receptor’s intracellular components sets off a chain of events that is called a signaling pathway or a signaling cascade. In a signaling pathway, second messengers, enzymes, and activated proteins interact with specific proteins, which are in turn activated in a chain reaction that eventually leads to a change in the cell’s environment. The events in the cascade occur in a series, much like a current flows in a river. Interactions that occur before a certain point are defined as upstream events, and events after that point are called downstream events.

Question 78

Why are signaling pathways complicated?

Answer 78

Signaling pathways can get very complicated very quickly because most cellular proteins can affect different downstream events, depending on the conditions within the cell. A single pathway can branch off toward different endpoints based on the interplay between two or more signaling pathways, and the same ligands are often used to initiate different signals in different cell types. This variation in response is due to differences in protein expression in different cell types. Another complicating element is signal integration of the pathways, in which signals from two or more different cell-surface receptors merge to activate the same response in the cell. This process can ensure that multiple external requirements are met before a cell commits to a specific response.

Question 79

How can signals be amplified?

Answer 79

The effects of extracellular signals can be amplified by enzymatic cascades. At the initiation of the signal, a single ligand binds to a single receptor. However, activation of a receptor-linked enzyme can activate many copies of a component of the signaling cascade, which amplifies the signal.

Question 80

What is phosphorylation?

Answer 80

One of the most common chemical modifications that occurs in signaling pathways is the addition of a phosphate group (PO₄^–3) to a molecule such as a protein in a process called phosphorylation.

Question 81

What are some examples of molecules that can be phosphorylated?

Answer 81

The phosphate can be added to a nucleotide such as GMP to form GDP or GTP. Phosphates are also often added to serine, threonine, and tyrosine residues of proteins, where they replace the hydroxyl group of the amino acid.

Question 82

What are some examples of the effects of phosphorylation?

Answer 82

Various kinases are named for the substrate they phosphorylate. Phosphorylation of serine and threonine residues often activates enzymes. Phosphorylation of tyrosine residues can either affect the activity of an enzyme or create a binding site that interacts with downstream components in the signaling cascade. Phosphorylation may activate or inactivate enzymes, and the reversal of phosphorylation, dephosphorylation by a phosphatase, will reverse the effect.

Question 83

What do second messengers do?

Answer 83

Second messengers are small molecules that propagate a signal after it has been initiated by the binding of the signaling molecule to the receptor. These molecules help to spread a signal through the cytoplasm by altering the behavior of certain cellular proteins.

Question 84

How is Ca²⁺ used as a second messenger?

Answer 84

Calcium ion is a widely used second messenger. The free concentration of calcium ions (Ca²⁺) within a cell is very low because ion pumps in the plasma membrane continuously use adenosine-5’-triphosphate (ATP) to remove it. For signaling purposes, Ca²⁺ is stored in cytoplasmic vesicles, such as the endoplasmic reticulum, or accessed from outside the cell. When signaling occurs, ligand-gated calcium ion channels allow the higher levels of Ca²⁺ that are present outside the cell (or in intracellular storage compartments) to flow into the cytoplasm, which raises the concentration of cytoplasmic Ca²⁺.

Question 85

How do cells respond to Ca²⁺ signaling?

Answer 85

The response to the increase in Ca²⁺ varies, depending on the cell type involved. For example, in the β-cells of the pancreas, Ca²⁺ signaling leads to the release of insulin, and in muscle cells, an increase in Ca²⁺ leads to muscle contractions.

Question 86

How is cAMP synthesized?

Answer 86

Cyclic AMP is synthesized by the enzyme adenylyl cyclase from ATP.

Question 87

What does cAMP-dependent kinase do?

Answer 87

A-kinase regulates many vital metabolic pathways: It phosphorylates serine and threonine residues of its target proteins, activating them in the process. A-kinase is found in many different types of cells, and the target proteins in each kind of cell are different. Differences give rise to the variation of the responses to cAMP in different cells.

Question 88

Where are inositol phospholipids located?

Answer 88

Because these molecules are membrane components, they are located near membrane-bound receptors and can easily interact with them.

Question 89

What does phosphatidylinositol do?

Answer 89

Phosphatidylinositol (PI) is the main phospholipid that plays a role in cellular signaling. Enzymes known as kinases phosphorylate PI to form PI-phosphate (PIP) and PI-bisphosphate (PIP₂).

Question 90

How is PIP₂ used in signal cascades?

Answer 90

The enzyme phospholipase C cleaves PIP₂ to form diacylglycerol (DAG) and inositol triphosphate (IP₃). These products of the cleavage of PIP₂ serve as second messengers. Diacylglycerol (DAG) remains in the plasma membrane and activates protein kinase C (PKC), which then phosphorylates serine and threonine residues in its target proteins. IP₃ diffuses into the cytoplasm and binds to ligand-gated calcium channels in the endoplasmic reticulum to release Ca²⁺ that continues the signal cascade.

Question 91

What is apoptosis?

Answer 91

Programmed cell death.

Question 92

What is a growth factor?

Answer 92

A ligand that binds to cell-surface receptors and stimulates cell growth.

Question 93

What is an inhibitor?

Answer 93

A molecule that binds to a protein (usually an enzyme) and keeps it from functioning.

Question 94

What is phosphatase?

Answer 94

An enzyme that removes the phosphate group from a molecule that has been previously phosphorylated.

Question 95

What is phosphodiesterase?

Answer 95

An enzyme that degrades cAMP, producing AMP, to terminate signaling.

Question 96

What is an example of a signaling pathway that regulates translation?

Answer 96

An example of a protein that regulates translation in the nucleus is the MAP kinase ERK. ERK is activated in a phosphorylation cascade when epidermal growth factor (EGF) binds the EGF receptor. Upon phosphorylation, ERK enters the nucleus and activates a protein kinase that, in turn, regulates protein translation.

Specifically, ERK is a MAP kinase that activates translation when it is phosphorylated. ERK phosphorylates MNK1, which in turn phosphorylates eIF-4E, an elongation initiation factor that, with other initiation factors, is associated with mRNA. When eIF-4E becomes phosphorylated, the mRNA unfolds, allowing protein synthesis in the nucleus to begin.

Question 97

What is an example of a signaling pathway that regulates transcription?

Answer 97

PKC can interact with an inhibitor protein called Iκ-B, which binds to the regulatory protein NF-κB. When Iκ-B is bound to NF-κB, the complex cannot enter the nucleus of the cell, but when Iκ-B is phosphorylated by PKC, it can no longer bind NF-κB, and NF-κB (a transcription factor) can enter the nucleus and initiate RNA transcription. In this case, the effect of phosphorylation is to inactivate an inhibitor and thereby activate the process of transcription.

Question 98

What is adrenaline?

Answer 98

Also known as epinephrine, adrenaline is a hormone (produced by the adrenal gland attached to the kidney) that readies the body for short-term emergencies.

Question 99

What happens during the signaling pathway triggered by adrenaline?

Answer 99

The result of another signaling pathway affects muscle cells. The activation of β-adrenergic receptors in muscle cells by adrenaline leads to an increase in cyclic AMP (cAMP) inside the cell. Cyclic AMP activates PKA (protein kinase A), which in turn phosphorylates two enzymes. The first enzyme promotes the degradation of glycogen by activating intermediate glycogen phosphorylase kinase (GPK) that in turn activates glycogen phosphorylase (GP) that catabolizes glycogen into glucose. Phosphorylation of the second enzyme, glycogen synthase (GS), inhibits its ability to form glycogen from glucose. In this manner, a muscle cell obtains a ready pool of glucose by activating its formation via glycogen degradation and by inhibiting the use of glucose to form glycogen, thus preventing a futile cycle of glycogen degradation and synthesis. The glucose is then available for use by the muscle cell in response to a sudden surge of adrenaline.

Question 100

What is an example of a signaling pathway that regulates cell division?

Answer 100

Cells do not normally divide unless they are stimulated by signals from other cells. Most growth factors bind to cell-surface receptors that are linked to tyrosine kinases. These cell-surface receptors are called receptor tyrosine kinases (RTKs). Activation of RTKs initiates a signaling pathway that includes a G-protein called RAS, which activates the ERK MAP kinase pathway to regulate translation. The enzyme MAP kinase then stimulates the expression of proteins that interact with other cellular components to initiate cell division.

Question 101

How can malfunctioning signaling pathways lead to cancer?

Answer 101

Signaling pathways control cell growth. These signaling pathways are controlled by signaling proteins, which are, in turn, expressed by genes. Mutations in these genes can result in malfunctioning signaling proteins. This prevents the cell from regulating its cell cycle, triggering unrestricted cell division and cancer. The genes that regulate the signaling proteins are one type of oncogene which is a gene that has the potential to cause cancer. If left unchecked, uncontrolled cell division can lead tumor formation and metastasis, the growth of cancer cells in new locations in the body.

Question 102

What is an example of an oncogene?

Answer 102

The gene encoding RAS is an oncogene that was originally discovered when mutations in the RAS protein were linked to cancer. Further studies have indicated that 30 percent of cancer cells have a mutation in the RAS gene that leads to uncontrolled growth.

Question 103

What is an example of an oncogene implicated in breast cancer and how can it be treated?

Answer 103

HER2 is a cell-surface receptor that is present in excessive amounts in 20 percent of human breast cancers. Cancer biologists realized that gene duplication led to HER2 overexpression in 25 percent of breast cancer patients and developed a drug called Herceptin (trastuzumab). Herceptin is a monoclonal antibody that targets HER2 for removal by the immune system. Herceptin therapy helps to control signaling through HER2. The use of Herceptin in combination with chemotherapy has helped to increase the overall survival rate of patients with metastatic breast cancer.

Question 104

Why do cells undergo apoptosis?

Answer 104

When a cell is damaged, superfluous, or potentially dangerous to an organism, a cell can initiate a mechanism to trigger programmed cell death, or apoptosis. Apoptosis allows a cell to die in a controlled manner that prevents the release of potentially damaging molecules from inside the cell. There are many internal checkpoints that monitor a cell’s health; if abnormalities are observed, a cell can spontaneously initiate the process of apoptosis. External signaling can also initiate apoptosis.

Question 105

Under what circumstances might apoptosis fail?

Answer 105

In some cases, such as a viral infection or uncontrolled cell division due to cancer, the cell’s normal checks and balances fail and apoptosis is not triggered.

Question 106

What is an example of apoptosis triggered by the extracellular matrix?

Answer 106

Most normal animal cells have receptors that interact with the extracellular matrix, a network of glycoproteins that provides structural support for cells in an organism. The binding of cellular receptors to the extracellular matrix initiates a signaling cascade within the cell. However, if the cell moves away from the extracellular matrix, the signaling ceases, and the cell undergoes apoptosis. This system keeps cells from traveling through the body and proliferating out of control, as happens with tumor cells that metastasize.

Question 107

What is an example of apoptosis triggered by the immune system?

Answer 107

Another example of external signaling that leads to apoptosis occurs in T-cell development. T-cells are immune cells that bind to foreign macromolecules and particles, and target them for destruction by the immune system. Normally, T-cells do not target “self” proteins (those of their own organism), a process that can lead to autoimmune diseases. In order to develop the ability to discriminate between self and non-self, immature T-cells undergo screening to determine whether they bind to so-called self proteins. If the T-cell receptor binds to self proteins, the cell initiates apoptosis to remove the potentially dangerous cell.

Question 108

What is an example of apoptosis triggered during embryological development?

Answer 108

Apoptosis is essential for normal embryological development. In vertebrates, for example, early stages of development include the formation of web-like tissue between individual fingers and toes. During the course of normal development, these unneeded cells must be eliminated, enabling fully separated fingers and toes to form. A cell signaling mechanism triggers apoptosis, which destroys the cells between the developing digits.

Question 109

How can signaling cascades be terminated?

Answer 109

One method of stopping a specific signal is to degrade the ligand or remove it so that it can no longer access its receptor.

Question 110

Why do hormones have longer-lasting effects?

Answer 110

One reason that hydrophobic hormones like estrogen and testosterone trigger long-lasting events is because they bind carrier proteins. These proteins allow the insoluble molecules to be soluble in blood, but they also protect the hormones from degradation by circulating enzymes.

Question 111

How can the effects of signaling cascades be reversed?

Answer 111

Inside the cell, many different enzymes reverse the cellular modifications that result from signaling cascades. For example, phosphatases are enzymes that remove the phosphate group attached to proteins by kinases in a process called dephosphorylation.

Question 112

What are some examples of signaling cascade reversal?

Answer 112

Cyclic AMP (cAMP) is degraded into AMP by phosphodiesterase, and the release of calcium stores is reversed by the Ca²⁺ pumps that are located in the external and internal membranes of the cell.

Question 113

What is an autoinducer?

Answer 113

A signaling molecule secreted by bacteria to communicate with other bacteria of its kind and others.

Question 114

What is a mating factor?

Answer 114

A signaling molecule secreted by yeast cells to communicate to nearby yeast cells that they are available to mate and communicating their mating orientation.

Question 115

What is quorum sensing?

Answer 115

A method of cellular communication used by bacteria that informs them of the abundance of similar (or different) bacteria in the environment.

Question 116

How are mating factors used during cell signaling in yeasts?

Answer 116

Yeasts are eukaryotes (fungi), and the components and processes found in yeast signals are similar to those of cell-surface receptor signals in multicellular organisms. Budding yeasts are able to participate in a process that is similar to sexual reproduction that entails two haploid cells combining to form a diploid cell. In order to find another haploid yeast cell that is prepared to mate, budding yeasts secrete a signaling molecule called mating factor. When mating factor binds to cell-surface receptors in other yeast cells that are nearby, they stop their normal growth cycles and initiate a cell signaling cascade that includes protein kinases and GTP-binding proteins that are similar to G-proteins.

Question 117

What are some circumstances in which bacteria signal to each other?

Answer 117

Signaling in bacteria enables bacteria to monitor extracellular conditions, ensure that there are sufficient amounts of nutrients, and ensure that hazardous situations are avoided.

Question 118

What was the first evidence for bacterial communication?

Answer 118

The first evidence of bacterial communication was observed in a bacterium that has a symbiotic relationship with Hawaiian bobtail squid. When the population density of the bacteria reaches a certain level, specific gene expression is initiated, and the bacteria produce bioluminescent proteins that emit light. Because the number of cells present in the environment (cell density) is the determining factor for signaling, bacterial signaling was named quorum sensing.

Question 119

How does quorum sensing work?

Answer 119

Quorum sensing uses autoinducers as signaling molecules. The secreted autoinducers can be small, hydrophobic molecules such as acyl-homoserine lactone, (AHL) or larger peptide-based molecules; each type of molecule has a different mode of action. When AHL enters target bacteria, it binds to transcription factors, which then switch gene expression on or off. The peptide autoinducers stimulate more complicated signaling pathways that include bacterial kinases. The changes in bacteria following exposure to autoinducers can be quite extensive. The pathogenic bacterium Pseudomonas aeruginosa has 616 different genes that respond to autoinducers.

Question 120

How does quorum sensing enable biofilms and what are their effects?

Answer 120

Some species of bacteria that use quorum sensing form biofilms, complex colonies of bacteria (often containing several species) that exchange chemical signals to coordinate the release of toxins that will attack the host. Bacterial biofilms can sometimes be found on medical equipment; when biofilms invade implants such as hip or knee replacements or heart pacemakers, they can cause life-threatening infections.

Question 121

How can quorum sensing be used for medical purposes?

Answer 121

Research on the details of quorum sensing has led to advances in growing bacteria for industrial purposes. Recent discoveries suggest that it may be possible to exploit bacterial signaling pathways to control bacterial growth; this process could replace or supplement antibiotics that are no longer effective in certain situations.

Question 122

How long did cellular communication take to evolve?

Answer 122

The first life on our planet consisted of single-celled prokaryotic organisms that had limited interaction with each other. While some external signaling occurs between different species of single-celled organisms, the majority of signaling within bacteria and yeasts concerns only other members of the same species. The evolution of cellular communication is an absolute necessity for the development of multicellular organisms, and this innovation is thought to have required approximately 2.5 billion years to appear in early life forms.

Question 123

How does the signaling complexity of yeasts compare to fruit flies and nematodes?

Answer 123

Comparisons of the genomes of yeasts, nematode worms, fruit flies, and humans illustrate the evolution of increasingly complex signaling systems that allow for the efficient inner workings that keep humans and other complex life forms functioning correctly.

Kinases are a major component of cellular communication, and studies of these enzymes illustrate the evolutionary connectivity of different species. Yeasts have 130 types of kinases. More complex organisms such as nematode worms and fruit flies have 454 and 239 kinases, respectively. Of the 130 kinase types in yeast, 97 belong to the 55 subfamilies of kinases that are found in other eukaryotic organisms.

Question 124

Why are yeasts used to study signaling pathways?

Answer 124

Because yeasts contain many of the same classes of signaling proteins as humans, these organisms are ideal for studying signaling cascades. Yeasts multiply quickly and are much simpler organisms than humans or other multicellular animals. Therefore, the signaling cascades are also simpler and easier to study, although they contain similar counterparts to human signaling.

The only obvious deficiency seen in yeasts is the complete absence of tyrosine kinases. It is hypothesized that phosphorylation of tyrosine residues is needed to control the more sophisticated functions of development, differentiation, and cellular communication used in multicellular organisms.