Question
The insulin receptor is a transmembrane protein that plays a role in the regulation of glucose homeostasis. The receptor’s extracellular domain binds specifically to the peptide hormone insulin. The receptor’s intracellular domain interacts with cellular factors. The binding of insulin to the receptor stimulates a signal transduction pathway that results in the subcellular translocation of GLUT4, a glucose transport protein that is stored in vesicles inside the cell. A simplified model of the insulin receptor–signaling pathway is shown in Figure 1.
Which of the following statements best predicts the effect of a loss of function of the insulin receptor’s intracellular domain?
A. The stimulation of the signal transduction pathway will increase.
B. The storage of GLUT4 in vesicles inside the cell will increase.
C. The number of GLUT4 molecules in the plasma membrane will increase.
D. The concentration of glucose inside the cell will increase.
▶️Answer/Explanation
Ans: B
The insulin receptor’s intracellular domain is required for the stimulation of the signal transduction pathway. If the signal transduction pathway is not stimulated by the insulin receptor, the GLUT4 vesicles will not be translocated to the plasma membrane. Consequently, the storage of GLUT4 in vesicles inside the cell will increase.
Question
The beta-2 adrenergic receptor is a membrane-bound protein that regulates several cellular processes, including the synthesis and breakdown of glycogen. The receptor binds specifically to the hormone epinephrine. The binding of epinephrine to the beta-2 adrenergic receptor triggers a signal transduction cascade that controls glycogen synthesis and breakdown in the cell. A simplified model of the signal transduction cascade is represented in Figure 1.
Which of the following outcomes will most likely result from the inactivation of the beta-2 adrenergic receptor?
A. The cellular concentration of cyclic AMP will increase.
B. The enzymatic activity of protein kinase A will increase.
C. The activation of glycogen phosphorylase will increase.
D. The rate of glycogen synthesis in the cell will increase.
▶️Answer/Explanation
Ans: D
Based on Figure 1, activation of the beta-2 adrenergic receptor results in the stimulation of glycogen breakdown and the inhibition of glycogen synthesis. The immediate effect of inactivating the beta-2 adrenergic receptor will be an increase in the rate of glycogen synthesis in the cell because glycogen synthase will no longer be inhibited. Also, glycogen breakdown in the cell will no longer be stimulated because glycogen phosphorylase will most likely be deactivated.
Question
Fibroblast growth factor receptors (FGFRs) are transmembrane proteins that regulate cellular processes such as cell proliferation and differentiation. The extracellular domains of FGFR proteins bind specifically to signaling molecules called fibroblast growth factors. The intracellular domains of FGFR proteins function as protein kinases, enzymes that transfer phosphate groups from ATP to protein substrates. FGFR activation occurs when binding by fibroblast growth factors causes FGFR proteins in the plasma membrane to become closely associated with each other. The association of two FGFR proteins stimulates protein kinase activity, which triggers the activation of intracellular signaling pathways. A simplified model of FGFR activation is represented in Figure 1.
Figure 1. A simplified model of FGFR activation
Which of the following changes in the FGFR signaling pathway is most likely to result in uncontrolled cell proliferation?
A. The irreversible association of FGFR proteins
B. The loss of the FGFR protein kinase function
C. A decrease in the intracellular concentration of ATP
D. A decrease in the extracellular concentrations of fibroblast growth factors
▶️Answer/Explanation
Ans: A
The irreversible association of FGFR proteins will most likely result in the permanent activation of the FGFR signaling pathway. Because the FGFR signaling pathway regulates cell proliferation, the irreversible association of FGFR proteins will result in uncontrolled cell proliferation.
Question
The epinephrine signaling pathway plays a role in regulating glucose homeostasis in muscle cells. The signaling pathway is activated by the binding of epinephrine to the beta-2 adrenergic receptor. A simplified model of the epinephrine signaling pathway is represented in Figure 1.
Figure 1. A simplified model of the epinephrine signaling pathway in muscle cells
Which of the following outcomes will most likely result from the irreversible binding of GDP to the G protein?
A. The intracellular concentration of glycogen will increase.
B. The intracellular concentration of activated protein kinase A will increase.
C. The intracellular concentration of cyclic AMP will increase.
D. The intracellular concentration of glucose-1-phosphate will increase.
▶️Answer/Explanation
Ans: A
Activation of the G protein requires the exchange of GDP for GTP. The irreversible binding of GDP to the G protein will block activation of the G protein, which will prevent epinephrine stimulation of glycogen breakdown. Consequently, the intracellular concentration of glycogen will increase.
Question
Glucocorticoids are steroid hormones that control cellular responses through several different signaling pathways. One of the signaling pathways involves the glucocorticoid receptor, an intracellular protein that is activated by binding to a glucocorticoid molecule. A simplified model of the glucocorticoid receptor signaling pathway is represented in Figure 1.
Figure 1. A simplified model of the glucocorticoid receptor signaling pathway
Which of the following statements best predicts the effect of a mutation that results in a loss of the glucocorticoid receptor’s ligand binding function?
A. The transduction of the glucocorticoid signal across the plasma membrane will be blocked.
B. The glucocorticoid receptor will remain associated with the accessory proteins.
C. The rate of diffusion of glucocorticoid molecules into the cell will increase.
D. The concentration of glucocorticoid receptors inside the nucleus will increase.
▶️Answer/Explanation
Ans: B
In the absence of glucocorticoid signaling, the glucocorticoid receptor is maintained in its inactive state in the cytosol by its association with accessory proteins. The binding of a glucocorticoid molecule to the glucocorticoid receptor induces a conformational change in the glucocorticoid receptor that results in its dissociation from the accessory proteins and translocation to the nucleus. A mutation that results in a loss of the glucocorticoid receptor’s ligand binding function will result in the glucocorticoid receptor remaining associated with the accessory proteins in a multiprotein complex in the cytosol.