AP Biology: Unit 4, Cell Communication (Drill 14)

Question 1. Based on the passage, which of the following correctly identifies the role of insulin in the signal transduction pathway described?

• A) It acts as a receptor, because it binds to the target cell surface and initiates the intracellular signaling cascade.
• B) It acts as a ligand, because it is a signaling molecule that binds to a receptor on the target cell surface to initiate the response. ✓
• C) It acts as a second messenger, because it carries the signal from the cell surface to the interior of the target cell within the described pathway.
• D) It acts as a protein kinase, because its binding triggers a phosphorylation cascade within the target cell.

Explanation: Correct: (B) A ligand is a signaling molecule that binds specifically to a receptor to initiate a cellular response. The passage states that insulin binds to a receptor tyrosine kinase on the outer surface of the target cell membrane. Insulin is the first messenger, the extracellular signal molecule, that triggers the pathway. It does not enter the cell, does not phosphorylate other proteins directly, and is not itself the receptor. Incorrect: (A) The receptor is the RTK located on the target cell surface. Insulin binds to the receptor but is not itself the receptor. A receptor receives and responds to the signal; a ligand is the signal molecule that binds to the receptor. Incorrect: (C) Second messengers are small intracellular molecules such as cAMP or calcium ions that relay and amplify the signal inside the cell after the receptor is activated. Insulin is an extracellular molecule that cannot cross the membrane and therefore cannot act as a second messenger. Incorrect: (D) Protein kinases phosphorylate other proteins. The passage states that the RTK (the receptor) phosphorylates itself and downstream targets, not that insulin performs the phosphorylation. Insulin triggers this activity by binding the RTK, but insulin itself is not a kinase.

Question 2. The passage describes that when blood glucose returns to the normal range after insulin is released, insulin secretion from beta cells decreases. Which of the following correctly identifies the type of feedback represented by this relationship and explains why?

• A) Negative feedback, because the response (decreased blood glucose via GLUT4 translocation) reduces the original stimulus (elevated blood glucose), which then reduces insulin secretion and dampens the initial signal. ✓
• B) Positive feedback, because insulin promotes glucose uptake, and increased glucose uptake causes more insulin to be secreted to further accelerate the process.
• C) Negative feedback, because decreasing insulin secretion is itself a negative event that simply reduces the amount of signaling molecule available to the target cells.
• D) Positive feedback, because the phosphorylation cascade within target cells amplifies the original insulin signal, which is a hallmark of positive feedback systems.

Explanation: Correct: (A) Negative feedback is a regulatory mechanism in which the output of a system reduces the original stimulus, returning conditions toward a set point. Here: elevated blood glucose (stimulus) triggers insulin release, which promotes GLUT4 translocation and glucose uptake (response), which reduces blood glucose (output). The reduced blood glucose then decreases insulin secretion, dampening the original signal. The system corrects itself by opposing the initial change, the definition of negative feedback. Incorrect: (B) If insulin promoted more insulin secretion, this would be positive feedback, a self-amplifying loop. The passage describes the opposite: when blood glucose returns to normal, insulin secretion decreases. The system is self-correcting, not self-amplifying. Incorrect: (C) Labeling the feedback as negative because insulin secretion 'decreases' (a negative event) confuses the sign of the output change with the classification of the feedback loop. Negative feedback is defined by the relationship between the stimulus and the response, not by whether a variable increases or decreases. Incorrect: (D) Signal amplification within the cell (via the phosphorylation cascade) describes how the signal is processed inside the cell, not the system-level feedback between blood glucose and insulin secretion. Intracellular cascade amplification is separate from the extracellular feedback loop described in the passage.

Question 3. A mutation causes the insulin receptor tyrosine kinase (RTK) to be produced in a structurally altered form that cannot undergo phosphorylation when insulin binds. Which of the following best predicts the consequence of this mutation for glucose uptake in affected muscle cells?

• A) Glucose uptake would increase, because without RTK phosphorylation the cell would use an alternative signaling pathway that more efficiently translocates GLUT4 to the membrane under the conditions described.
• B) Glucose uptake would be unaffected, because GLUT4 translocates to the plasma membrane independently of insulin signaling in resting skeletal muscle cells.
• C) Glucose uptake would decrease, because without RTK phosphorylation the downstream signaling cascade cannot be initiated, preventing GLUT4 from translocating to the plasma membrane. ✓
• D) Glucose uptake would initially decrease but then recover, because beta cells would compensate by secreting more insulin to overcome the receptor defect.

Explanation: Correct: (C) The passage describes a linear signaling sequence: insulin binds RTK, RTK phosphorylates itself and downstream proteins, phosphorylation cascade occurs, GLUT4 translocates to the plasma membrane, glucose enters the cell. If the RTK cannot be phosphorylated, the entire downstream cascade is blocked at the first step. Without the cascade, GLUT4 remains sequestered in intracellular vesicles and cannot reach the plasma membrane. Therefore glucose uptake by the affected muscle cells would decrease, because the transporter proteins needed to import glucose would not be available at the cell surface. Incorrect: (A) The passage describes no alternative pathway for GLUT4 translocation in muscle cells. Proposing an alternative pathway introduces a mechanism not supported by the stimulus. In the absence of functional RTK signaling, there is no described compensatory route. Incorrect: (B) The passage directly states that GLUT4 translocation is an outcome of the RTK phosphorylation cascade. GLUT4 is stored in intracellular vesicles and is brought to the membrane in response to insulin signaling. Without that signal, GLUT4 does not translocate. Incorrect: (D) Secreting more insulin cannot overcome a non-functional receptor. If the RTK cannot be phosphorylated regardless of how much insulin binds, increasing insulin concentration does not restore the cascade. The defect is in the receptor's catalytic activity, not in ligand availability.

Question 4. The passage notes that insulin signaling activates transcription factors that increase expression of genes involved in glucose metabolism. If the insulin signaling pathway is activated in a target cell, which of the following sequences of events best represents the complete pathway from insulin binding to increased gene expression?

• A) Insulin binds GLUT4, GLUT4 translocates to the membrane, glucose enters, glucose activates transcription factors, gene expression increases.
• B) Insulin binds RTK, RTK is phosphorylated, GLUT4 translocates to the membrane, GLUT4 then enters the nucleus and directly activates transcription of glucose metabolism genes.
• C) Insulin is transported into the nucleus, insulin binds directly to promoter regions of target genes, transcription of glucose metabolism genes increases.
• D) Insulin binds RTK on the plasma membrane, RTK initiates a phosphorylation cascade, downstream proteins in the cascade activate transcription factors, transcription factors increase expression of glucose metabolism genes. ✓

Explanation: Correct: (D) The passage describes the following sequence: insulin (a peptide hormone that cannot cross the membrane) binds the RTK on the outer plasma membrane surface, triggering RTK self-phosphorylation and a downstream phosphorylation cascade. The passage then states that insulin signaling activates transcription factors that increase gene expression. This correctly represents a receptor-mediated signal transduction pathway in which an extracellular signal is relayed through intracellular intermediaries to ultimately alter gene expression, without the ligand itself ever entering the cell. Incorrect: (A) Insulin does not bind GLUT4. GLUT4 is a glucose transporter protein, not an insulin receptor. Insulin binds the RTK. Glucose entry into the cell is a consequence of GLUT4 translocation, not a cause of transcription factor activation in the pathway described. Incorrect: (B) GLUT4 is a plasma membrane transporter protein, not a transcription factor, and does not enter the nucleus. GLUT4 translocates from intracellular vesicles to the plasma membrane to facilitate glucose transport. Describing GLUT4 entering the nucleus and activating transcription is mechanistically incorrect. Incorrect: (C) The passage explicitly states that insulin cannot cross the plasma membrane. Peptide hormones are too large and hydrophilic to cross the lipid bilayer and therefore cannot enter the nucleus or bind directly to DNA. This sequence describes steroid hormone signaling, not peptide hormone signaling.

Question 5. A researcher treats muscle cells in culture with a drug that irreversibly blocks all RTK phosphorylation activity in those cells. The cells are then exposed to a high concentration of insulin for 30 minutes, followed by normal insulin concentration for 60 more minutes. Which of the following best predicts the effect on glucose uptake in the treated muscle cells over this entire 90-minute period?

• A) Glucose uptake will remain normal throughout the period because muscle cells have alternative insulin-independent uptake mechanisms that fully replace the blocked RTK pathway.
• B) Glucose uptake will remain reduced throughout the 90-minute period because without functional RTK phosphorylation, GLUT4 cannot translocate to the plasma membrane regardless of insulin concentration. ✓
• C) Glucose uptake will be reduced for the first 30 minutes but will recover during the final 60 minutes as insulin concentration decreases and the drug block is relieved.
• D) Glucose uptake will increase above normal during the first 30 minutes because high insulin concentration overwhelms the drug block, then return to baseline when insulin concentration decreases over the treatment period described.

Explanation: Correct: (B) The drug irreversibly blocks all RTK phosphorylation. Without RTK phosphorylation, the downstream cascade cannot be initiated and GLUT4 cannot translocate to the plasma membrane. This block is irreversible; it persists regardless of insulin concentration or time. Therefore glucose uptake in the treated cells will remain reduced throughout the entire 90-minute period, because the signaling machinery required to bring GLUT4 to the membrane is permanently disabled. Changing the insulin concentration in the medium has no effect on a receptor that cannot be activated. Incorrect: (A) The passage describes no alternative insulin-independent pathway for GLUT4 translocation. While some basal glucose uptake may occur through other transporters, GLUT4-mediated insulin-stimulated uptake is blocked, and glucose uptake will remain below normal. Incorrect: (C) The block is irreversible, not concentration-dependent. Reducing insulin concentration during the final 60 minutes does not restore RTK function or relieve the drug's effect. The phosphorylation block persists regardless of how much or how little insulin is present. Incorrect: (D) An irreversible block cannot be overcome by increasing ligand concentration. The drug permanently inactivates the RTK's phosphorylation activity. No amount of insulin binding to the receptor can restore the catalytic function the drug has destroyed.