This section contains 20 multiple-choice questions. For questions 1-18 and 20, select the one best answer from the four choices provided. For questions 19, select the two best answers as indicated. Each multiple-choice question is worth 1 point. You may use a calculator on this section.
A researcher is studying signal transduction in neurons. She observes that when neurotransmitter molecules bind to receptors on the postsynaptic membrane, ion channels open and allow sodium ions to flow into the cell. This change in ion concentration leads to depolarization of the membrane.
Which type of receptor is most likely involved in this process?
When insulin binds to its receptor on a muscle cell:
Based on the pathway shown, the insulin receptor is best classified as which type of receptor?
Epinephrine binding to a G protein-coupled receptor on a liver cell leads to the activation of adenylyl cyclase, which converts ATP to cyclic AMP (cAMP). One molecule of epinephrine binding to the receptor can result in the production of hundreds of cAMP molecules.
This observation best illustrates which concept in cell communication?
A biologist measures the concentration of cAMP in cells exposed to a hormone at different time points:

Which statement best explains the decrease in cAMP concentration observed between 30 and 60 seconds?
Testosterone is a steroid hormone that regulates gene expression in target cells. Unlike peptide hormones such as insulin, testosterone can pass directly through the plasma membrane.
Which property of testosterone best explains its ability to cross the plasma membrane?
Researchers create three groups of cultured cells:
All groups are exposed to a growth factor, and cell proliferation is measured after 48 hours.
Which prediction about cell proliferation is most likely correct?
In many signaling pathways, protein kinases transfer phosphate groups from ATP to specific amino acids on target proteins, thereby activating or deactivating those proteins. Protein phosphatases remove these phosphate groups.
What is the primary role of protein phosphatases in cell signaling?

Based on the data, which conclusion about cell communication is most strongly supported?
Quorum sensing is a form of cell-to-cell communication used by many bacterial species. Bacteria release signaling molecules called autoinducers into their environment. When the population density reaches a threshold level, the concentration of autoinducers becomes high enough to activate specific genes in the bacterial cells.
Which statement best describes the adaptive advantage of quorum sensing?
Scientists studying apoptosis (programmed cell death) expose cells to different concentrations of a death signal molecule. They measure the percentage of cells that undergo apoptosis after 24 hours:

Which statement is best supported by these data?
Gap junctions are protein channels that directly connect the cytoplasm of adjacent animal cells, allowing small molecules and ions to pass between cells. Plasmodesmata serve a similar function in plant cells.
A researcher treats a tissue with a drug that blocks gap junctions. Which cellular process would be most directly disrupted?
A signal molecule binds to a receptor tyrosine kinase (RTK) on the cell surface. The following cascade occurs:
A mutation in the Ras protein causes it to remain in the active state even in the absence of a signal. What is the most likely consequence of this mutation?
In pancreatic beta cells, an increase in blood glucose concentration leads to glucose uptake and metabolism. This increases the ATP/ADP ratio in the cell, which causes ATP-sensitive potassium channels to close. The resulting change in membrane potential triggers calcium channels to open, and the influx of calcium ions stimulates the release of insulin.
In this example, what serves as the initial signal that triggers the response?
Cells are exposed to varying concentrations of a signaling molecule, and the cellular response is measured. The graph shows:
The plateau in the response at high concentrations of the signaling molecule is most likely due to which phenomenon?
Acetylcholine is a neurotransmitter released at the synapse between a motor neuron and a muscle cell. After acetylcholine binds to receptors on the muscle cell and triggers a response, the enzyme acetylcholinesterase rapidly breaks down acetylcholine in the synaptic cleft.
What is the primary function of acetylcholinesterase in this system?
Scientists investigate whether two different signaling pathways interact. They treat cells with:
Which conclusion is best supported by these experimental results?
Nitric oxide (NO) is a small, uncharged molecule that acts as a local regulator in animal tissues. Unlike most signaling molecules, NO is not stored in cells but is synthesized on demand. It diffuses readily across membranes and has a very short half-life (a few seconds).
Which characteristic of nitric oxide makes it particularly suited for paracrine signaling rather than endocrine signaling?
Researchers measure the density of epidermal growth factor (EGF) receptors on three cell lines and their proliferation rate in response to EGF treatment:

Note: In the absence of EGF, all three cell lines divide approximately 0.4 times per 24 hours.
Based on these data, which statement represents the most reasonable interpretation?
Select TWO answers. In yeast cells, mating factors are signaling molecules that bind to receptors on cells of the opposite mating type. This binding triggers a signal transduction pathway that prepares the cells to fuse. The pathway involves G proteins, kinases, and transcription factors.
Which TWO statements accurately describe components or principles of this signaling system?
The mitogen-activated protein kinase (MAPK) pathway is involved in regulating cell division. Scientists develop a drug that specifically inhibits MEK, a kinase in this pathway. They test the drug on cancer cells that have overactive RTK signaling.
Results:
Which explanation best accounts for the effect of the MEK inhibitor on cancer cell division?
This section contains 2 free-response questions. Answer all parts of each question completely. Where calculations are required, clearly show your work. Where explanation or discussion is required, support your answers with relevant evidence and logical reasoning. Write your responses in complete sentences.
Epinephrine is a hormone that helps regulate the body's response to stress. When epinephrine binds to beta-adrenergic receptors on liver cells, it triggers a signal transduction pathway that ultimately leads to the breakdown of glycogen into glucose. This pathway involves multiple steps of signal amplification.
(a) Identify the second messenger in this signal transduction pathway.
(b) Describe how signal amplification occurs at the adenylyl cyclase step of this pathway.
(c) Scientists investigate the role of phosphodiesterase, an enzyme that breaks down cAMP into AMP, by conducting an experiment. They treat liver cells with epinephrine and measure glucose production over time under two conditions:

(i) Calculate the average rate of glucose production (in μmol/L per minute) for normal cells between 10 and 20 minutes.
(ii) Based on the data, explain how phosphodiesterase affects the duration of the cellular response to epinephrine.
(d) A mutation in the gene encoding the G protein results in a version that cannot hydrolyze GTP to GDP. Predict the effect of this mutation on glucose production in liver cells, even in the absence of epinephrine. Justify your prediction.
(e) Design an experiment to determine whether caffeine increases the duration of the epinephrine response by inhibiting phosphodiesterase. Your description should include:
(f) Explain how the epinephrine signaling pathway in liver cells illustrates the concept that cellular responses to signals depend on the specific proteins present in the target cell.
Cell communication can occur through different mechanisms depending on the distance between the signaling cell and the target cell. Three major types of signaling are:
(a) Identify which type of cell signaling (endocrine, paracrine, or direct contact) is represented in Scenario 1.
(b) Explain why paracrine signaling (Scenario 2) is more appropriate than endocrine signaling for rapid, localized immune responses.
(c) The signaling molecule in Scenario 2 (cytokines) is composed of amino acids and cannot cross plasma membranes. Based on this information, describe where the receptors for cytokines are most likely located and justify your answer.
(d) Predict what would happen to coordination of the heartbeat if a drug blocked gap junctions between heart muscle cells (Scenario 1). Justify your prediction.

Cyclic AMP (cAMP) is the second messenger in this signal transduction pathway. It is produced from ATP by adenylyl cyclase and carries the signal from the membrane-associated enzyme into the cytoplasm, where it activates protein kinase A.
Signal amplification at the adenylyl cyclase step occurs because one activated adenylyl cyclase enzyme can catalyze the conversion of many ATP molecules into cAMP molecules. A single activated G protein can keep adenylyl cyclase active for a period of time, during which hundreds or thousands of cAMP molecules are produced. This means that the binding of a single epinephrine molecule to one receptor can result in the production of many second messenger molecules, thereby amplifying the initial signal.
The average rate of glucose production for normal cells between 10 and 20 minutes is calculated as follows:
\[ \text{Rate} = \frac{\Delta \text{[glucose]}}{\Delta \text{time}} = \frac{192 - 145}{20 - 10} = \frac{47}{10} = 4.7 \text{ μmol/L per minute} \]
Answer: 4.7 μmol/L per minute
The data show that cells treated with a phosphodiesterase inhibitor produce significantly more glucose over time compared to normal cells. By 30 minutes, inhibitor-treated cells produce 562 μmol/L glucose compared to 198 μmol/L in normal cells. Additionally, glucose production in normal cells begins to plateau after 20 minutes, while production in inhibitor-treated cells continues to increase.
This indicates that phosphodiesterase normally limits the duration of the cellular response by breaking down cAMP. When phosphodiesterase is inhibited, cAMP accumulates to higher levels and persists longer, prolonging the activation of protein kinase A and downstream enzymes, which results in sustained glucose production. Therefore, phosphodiesterase acts as a negative regulator that terminates the signal.
Prediction: The mutation would cause glucose production to occur continuously, even in the absence of epinephrine, resulting in chronically elevated blood glucose levels.
Justification: The G protein normally cycles between an inactive state (bound to GDP) and an active state (bound to GTP). The active form stimulates adenylyl cyclase to produce cAMP. The G protein's intrinsic GTPase activity hydrolyzes GTP to GDP, returning the protein to its inactive state and turning off the signal. If the mutant G protein cannot hydrolyze GTP, it will remain permanently in the active state, continuously activating adenylyl cyclase and producing cAMP. This will lead to constant activation of protein kinase A and the downstream glycogen breakdown pathway, causing unregulated glucose production regardless of epinephrine levels.
A complete experimental design should include:
Independent variable: Presence or absence of caffeine
Dependent variable: Duration and magnitude of glucose production following epinephrine treatment
Experimental procedure:
Expected results that would support the hypothesis: If caffeine inhibits phosphodiesterase, cells treated with caffeine should show higher glucose production that persists for a longer time period compared to control cells. The glucose production curve for caffeine-treated cells should remain elevated while the control group returns to baseline more quickly, similar to the pattern observed with the phosphodiesterase inhibitor in part (c).
Expected results that would refute the hypothesis: If glucose production shows the same time course and magnitude in both groups, this would suggest caffeine does not inhibit phosphodiesterase in this system.
The epinephrine signaling pathway in liver cells illustrates that cellular responses to signals depend on the specific proteins present in the target cell in several ways:
First, only cells with beta-adrenergic receptors can respond to epinephrine in this manner. Cells lacking these receptors will not respond to the hormone, even if it is present at high concentrations. This explains why epinephrine has different effects on different tissues.
Second, the presence of specific intracellular proteins (G proteins, adenylyl cyclase, protein kinase A, phosphorylase kinase, and glycogen phosphorylase) in liver cells allows them to convert the epinephrine signal into glycogen breakdown. Other cell types with the same receptor but different downstream proteins might respond to epinephrine by altering different cellular processes (e.g., heart muscle cells respond with increased contraction rate).
This demonstrates the principle that the same signaling molecule can produce different responses in different cell types based on the complement of receptors and signal transduction proteins that each cell expresses. Cell specialization is therefore achieved not only by which signals cells receive, but by how they interpret and respond to those signals based on their unique protein expression profiles.
Direct contact signaling (also acceptable: cell-to-cell signaling via gap junctions)
In Scenario 1, heart muscle cells communicate through gap junctions, which create direct cytoplasmic connections between adjacent cells, allowing ions and small molecules to pass directly from one cell to another without crossing extracellular space.
Paracrine signaling is more appropriate than endocrine signaling for rapid, localized immune responses because paracrine signals act on nearby cells within a localized region, whereas endocrine signals must travel through the circulatory system to reach distant targets.
When an infection occurs at a specific site, immune cells need to quickly alert and recruit other immune cells to that precise location. Paracrine signaling allows cytokines released by immune cells to rapidly diffuse short distances to affect only neighboring cells, creating a concentrated, localized response at the site of infection. This limits inflammation and immune activity to where it is needed.
In contrast, endocrine signaling would distribute the signal throughout the entire body via the bloodstream, which would be slower, less efficient, and could trigger unnecessary systemic responses in tissues far from the infection site. The short range and rapid action of paracrine signals make them ideal for coordinating localized responses.
Cytokine receptors are most likely located on the cell surface (plasma membrane), specifically as integral membrane proteins with their binding domains facing the extracellular environment.
Justification: Because cytokines are composed of amino acids (making them proteins or peptides) and cannot cross the hydrophobic lipid bilayer of the plasma membrane, they must bind to receptors on the exterior surface of target cells. Hydrophilic signaling molecules like proteins require cell-surface receptors because they cannot diffuse through the membrane to reach intracellular receptors. Only small, lipid-soluble (hydrophobic) molecules such as steroid hormones can pass through membranes and bind to intracellular receptors. Therefore, cytokines must interact with transmembrane receptor proteins that can relay the signal from the outside of the cell to the inside through conformational changes and subsequent activation of intracellular signaling pathways.
Prediction: Blocking gap junctions between heart muscle cells would disrupt the coordinated contraction of the heart, leading to irregular or ineffective heartbeats (arrhythmia) and potentially causing the heart to fail to pump blood effectively.
Justification: The coordinated heartbeat depends on the rapid propagation of electrical signals (in the form of ion flows) from one heart muscle cell to the next through gap junctions. When one cell depolarizes, ions flow through gap junctions to depolarize adjacent cells in a wave-like pattern. This synchronized depolarization causes all cells in a region to contract nearly simultaneously, producing the forceful, coordinated contraction needed to pump blood efficiently. If gap junctions are blocked, electrical signals cannot pass between cells. Each cell would contract independently based only on signals it receives directly, destroying the coordinated timing necessary for effective pumping. The heart chambers would contract irregularly or not at all, severely compromising cardiac function.