- In a study of hepatocytes, investigators perfused cells with a peptide hormone (H) that does not cross the plasma membrane. Within 60 seconds, intracellular cAMP increased ~6-fold and phosphorylation of a cytosolic enzyme increased. When cells were pretreated with a competitive antagonist to the H receptor, both the cAMP rise and enzyme phosphorylation were abolished. The investigators note that H circulates largely unbound in plasma and has a short half-life.
Which outcome would be expected if the receptor is blocked, as in the antagonist condition?
Answer: Reduced activation of protein kinase A and reduced phosphorylation of downstream cytosolic targets
This question tests understanding of GPCR signal transduction, specifically how blocking a receptor affects downstream signaling through the cAMP pathway. In GPCR signaling, hormone binding activates the receptor, which then activates a G protein that stimulates adenylyl cyclase to produce cAMP, which in turn activates protein kinase A (PKA) to phosphorylate target proteins. The passage describes a peptide hormone that increases cAMP and enzyme phosphorylation, classic hallmarks of Gs-coupled GPCR signaling. When the receptor is blocked by an antagonist, the entire cascade is prevented: no receptor activation means no G protein activation, no adenylyl cyclase stimulation, no cAMP production, and therefore no PKA activation. The correct answer B accurately describes this outcome - reduced PKA activation and reduced phosphorylation of downstream targets. Choice A incorrectly describes nuclear receptor signaling (which requires membrane-permeable hormones), while choices C and D describe different signaling pathways (Gq/PLC/IP3 and receptor tyrosine kinase pathways, respectively) that are not consistent with the cAMP response described.
- A researcher applied insulin to skeletal muscle cells and observed increased phosphorylation of a membrane-proximal adaptor protein followed by increased translocation of GLUT4 to the plasma membrane. A pharmacologic inhibitor prevented receptor autophosphorylation on tyrosine residues. Which outcome would be expected if the receptor is blocked?
Answer: Decreased GLUT4 translocation due to reduced downstream signaling from the receptor
This question assesses hormone transport, receptors, and signal transduction, highlighting insulin's RTK pathway in muscle. Signal transduction starts with autophosphorylation, activating adaptors for GLUT4 translocation. Insulin binds RTK, phosphorylating adaptors to mobilize GLUT4. Receptor blockade reduces signaling and translocation, per choice D. Choice B suggests increased activity from dephosphorylation loss, but blockade prevents initiation. For related queries, identify RTK by tyrosine motifs. Examine inhibitor effects on proximal events.
- A receptor tyrosine kinase (RTK) ligand (F) is added to epithelial cells. Within 5 minutes, ERK phosphorylation increases. After 60 minutes, expression of cyclin D increases. A small-molecule inhibitor that blocks RTK dimerization prevents ERK phosphorylation and cyclin D induction. A separate inhibitor that blocks MEK (upstream of ERK) prevents ERK phosphorylation and cyclin D induction but does not prevent RTK autophosphorylation.
Which step is most directly prevented by the RTK dimerization inhibitor?
Answer: Autophosphorylation of tyrosine residues on the RTK cytosolic tails following receptor pairing
This question tests understanding of receptor tyrosine kinase (RTK) signal transduction, specifically the critical role of receptor dimerization in initiating downstream signaling cascades. Signal transduction through RTKs requires ligand binding to induce receptor dimerization, which enables trans-autophosphorylation of tyrosine residues on the cytoplasmic tails, creating docking sites for downstream signaling proteins. The dimerization inhibitor prevents RTK pairing and thus blocks all downstream events (ERK phosphorylation and cyclin D expression), while the MEK inhibitor only blocks steps downstream of RTK activation. Option B correctly identifies that autophosphorylation following receptor pairing is the step directly prevented by the dimerization inhibitor. The distractor A (ligand binding) occurs before dimerization, while C incorrectly invokes steroid signaling, and D suggests an incorrect PLC-based mechanism for RTK signaling. To solve RTK questions, remember the canonical sequence: ligand binding → dimerization → autophosphorylation → adaptor protein recruitment → downstream kinase cascades, and recognize that blocking dimerization prevents all phosphorylation events.
- A lab compared signaling from two hormones in the same cell type. Hormone X is lipid-soluble and circulates largely bound to a plasma carrier protein; hormone Y is water-soluble and circulates mostly free. In cells, X produced changes in mRNA abundance after 2 hours, while Y produced increased phosphorylation of a cytosolic protein within 1 minute. Which statement best distinguishes the receptor location and initial signaling mechanism for X versus Y?
Answer: X binds an intracellular receptor that regulates transcription; Y binds a cell-surface receptor that initiates second messengers
This question probes hormone transport, receptors, and signal transduction, contrasting lipid- and water-soluble hormone mechanisms. Signal transduction differs by receptor location: intracellular for lipid-soluble, surface for water-soluble, leading to transcriptional or rapid phosphorylation changes. Hormone X, lipid-soluble and carrier-bound, acts via intracellular receptors for slow mRNA effects, while Y uses surface receptors for quick phosphorylation. Choice B correctly distinguishes these, with X regulating transcription and Y initiating second messengers. Choice A reverses the mechanisms, a common mix-up flaw. For parallels, note solubility and timing to infer receptor type. Evaluate carrier protein roles in transport equilibrium.
- A peptide hormone (H) binds a GPCR on cardiomyocytes and increases contractility. Inhibiting phosphodiesterase (PDE) prolonged the H-induced increase in cAMP but did not alter receptor binding affinity. Based on the scenario, which step is most likely influenced by external factors (e.g., PDE inhibition)?
Answer: Degradation of cAMP, thereby altering the duration of second-messenger signaling
This question assesses hormone transport, receptors, and signal transduction, emphasizing second-messenger regulation in cardiac cells. Signal transduction includes cAMP production and degradation by PDEs, modulating signal duration. Hormone H activates GPCR, increasing cAMP for contractility, with PDE inhibition prolonging effects. Choice B identifies cAMP degradation as influenced by PDE inhibition, consistent with unchanged binding. Choice A distracts with initial binding, unaffected by PDE. In related questions, note enzymes regulating messenger levels. Evaluate inhibitor impacts on signal kinetics.
- A growth factor (GF) is added to a fibroblast line expressing its cognate RTK. Within 2 minutes, the receptor becomes phosphorylated on tyrosine residues and a downstream kinase shows increased phosphorylation. In a mutant cell line, the RTK retains normal ligand binding but lacks the intracellular tyrosine kinase domain. Both lines are exposed to identical GF concentrations.
Which cellular response is most consistent with the signal transduction pathway described in the mutant line?
Answer: Reduced downstream kinase phosphorylation despite normal GF binding at the cell surface
This question tests understanding of RTK signal transduction, specifically the requirement for the intracellular tyrosine kinase domain in propagating growth factor signals through autophosphorylation and downstream kinase activation. RTKs function by ligand-induced dimerization, which brings together intracellular kinase domains that trans-phosphorylate each other on tyrosine residues, creating docking sites for adaptor proteins that activate downstream kinases. In this scenario, the mutant RTK lacks the tyrosine kinase domain, so despite normal growth factor binding at the cell surface, it cannot undergo autophosphorylation or activate downstream signaling cascades. The correct answer B accurately predicts reduced downstream kinase phosphorylation despite normal GF binding, because the kinase domain is essential for signal propagation beyond the receptor. A common distractor (A) incorrectly suggests that ligand binding alone is sufficient for signaling, ignoring the critical role of the kinase domain in RTK function. When analyzing RTK signaling questions, remember that the intracellular kinase domain is absolutely required for autophosphorylation and downstream signaling, making it a key structural feature that distinguishes functional from non-functional receptors.
- Two hormones, A and B, each increase glycogen breakdown in hepatocytes but via different receptors. Hormone A binds a GPCR coupled to Gs and increases cAMP, activating PKA. Hormone B binds a receptor tyrosine kinase (RTK), leading to autophosphorylation and recruitment of cytosolic adaptor proteins that activate a kinase cascade. Inhibiting adenylyl cyclase prevents A-induced glycogen breakdown but does not affect B-induced glycogen breakdown.
Which outcome would be expected if the RTK for hormone B is blocked while hormone A signaling remains intact?
Answer: Loss of B-induced glycogen breakdown with preserved A-induced glycogen breakdown
This question tests understanding of distinct signal transduction pathways - GPCR-cAMP versus RTK cascades - and their independence in mediating hormone responses like glycogen breakdown. Hormone A uses a GPCR-Gs-cAMP-PKA pathway while hormone B uses an RTK-kinase cascade pathway, representing two major but separate signaling mechanisms that can achieve similar cellular outcomes through different molecular intermediates. In this scenario, blocking the RTK for hormone B would specifically prevent B-induced glycogen breakdown by disrupting its unique signaling cascade, while leaving the A pathway intact since it operates through entirely different molecular components. The correct answer D accurately predicts loss of B-induced glycogen breakdown with preserved A-induced glycogen breakdown, reflecting the independence of these two pathways. A common distractor (B) incorrectly suggests that RTKs are required for GPCR signaling, when in fact these are completely separate receptor systems with distinct downstream effectors. When analyzing questions involving multiple hormone pathways, identify whether they use the same or different receptor types and signaling cascades to predict how selective inhibition will affect each response independently.
- Researchers study a peptide hormone (P) that binds a cell-surface GPCR on renal collecting duct cells. In the presence of P, intracellular cAMP increases and a water channel is redistributed from intracellular vesicles to the apical membrane within 10 minutes. In a follow-up experiment, cells are exposed to a nonhydrolyzable GDP analog that locks heterotrimeric G proteins in their inactive state, without altering receptor expression or P binding affinity.
Based on the scenario, which step is most likely to be influenced by the GDP analog?
Answer: Exchange of GDP for GTP on the Gα subunit
This question tests understanding of GPCR signal transduction, specifically the role of GTP/GDP exchange in G protein activation during hormone-induced water channel redistribution. GPCRs activate heterotrimeric G proteins by catalyzing the exchange of GDP for GTP on the Gα subunit, which is the key activation step that allows the G protein to dissociate and activate downstream effectors like adenylyl cyclase. In this scenario, peptide hormone P binds its GPCR, leading to G protein activation, increased cAMP, and water channel insertion into the apical membrane. The nonhydrolyzable GDP analog locks G proteins in their inactive GDP-bound state, preventing the GDP-to-GTP exchange that is essential for G protein activation. The correct answer B identifies that the GDP analog would influence the exchange of GDP for GTP on the Gα subunit, effectively blocking signal transduction at this critical step. A common distractor (A) incorrectly focuses on ligand binding, which would not be affected by the GDP analog since it acts on the G protein, not the receptor. When analyzing GPCR pathways, remember that the GDP/GTP exchange is the rate-limiting step in G protein activation and represents a key regulatory point in the signaling cascade.
- A peptide hormone (K) is infused into an animal. Plasma measurements show that total K concentration remains high, but target tissue responses decline over 2 hours. Biopsy of target cells shows decreased receptor density at the plasma membrane and increased receptor signal in endosomal compartments. Intracellular second messenger production in response to an acute K bolus is reduced compared with baseline.
Based on the scenario, which step is most likely to be influenced by external factors leading to the observed decline in response?
Answer: Receptor internalization from the plasma membrane, reducing the number of receptors available for K binding
This question tests understanding of receptor desensitization as a regulatory mechanism in hormone signal transduction, specifically how sustained hormone exposure leads to receptor internalization and reduced cellular responsiveness. Signal transduction is dynamically regulated, with cells modulating their sensitivity through receptor trafficking: prolonged agonist exposure triggers receptor phosphorylation, β-arrestin binding, and endocytosis, removing receptors from the cell surface. The experimental observations - maintained high plasma K levels but declining tissue responses, decreased surface receptors, increased endosomal receptors, and reduced acute signaling - all point to receptor internalization (option B) as the mechanism. This represents classic GPCR desensitization where the external factor (sustained hormone exposure) drives compensatory receptor downregulation. The distractor C incorrectly suggests passive diffusion for a peptide hormone, while D proposes increased transcription contradicting the observed decrease in surface receptors. To identify desensitization in similar scenarios, look for the combination of sustained stimulus, declining response despite maintained hormone levels, and evidence of receptor redistribution from surface to intracellular compartments.
- A lab studies the effect of a peptide hormone (G) on hepatocyte glycogen breakdown. G treatment increases glycogen phosphorylase activity within 1 minute. Inhibiting PKA blocks this increase. Inhibiting phosphodiesterase (PDE) prolongs the effect of G, while inhibiting protein phosphatase 1 (PP1) increases basal glycogen phosphorylase activity even without G.
Which outcome would be expected if the receptor for G is blocked, but PDE is simultaneously inhibited?
Answer: No activation of glycogen phosphorylase because blocking the receptor prevents the upstream rise in cAMP that PDE inhibition would otherwise prolong
This question tests understanding of hormone receptor blockade effects on signal transduction cascades, specifically how phosphodiesterase inhibition cannot rescue signaling when upstream receptor activation is prevented. Signal transduction through GPCRs requires sequential activation: receptor binding → G protein activation → adenylyl cyclase activation → cAMP production → PKA activation → substrate phosphorylation. The scenario shows that hormone G activates glycogen phosphorylase through a cAMP-PKA pathway, with PDE normally degrading cAMP to terminate the signal. When the G receptor is blocked, no initial cAMP is produced for PDE inhibition to preserve, making option B correct - there's no upstream signal to prolong. The distractor A incorrectly assumes PDE inhibition can generate cAMP independently, but PDE only degrades existing cAMP, not create it. To approach similar problems, trace the signaling cascade and recognize that downstream manipulations (like PDE inhibition) cannot compensate for blocked upstream events (receptor activation) - you need initial signal generation for amplification or prolongation to matter.
- Two hormones regulate water handling in collecting duct principal cells. Hormone V causes insertion of aquaporin-2 (AQP2) channels into the apical membrane within 10 minutes. Hormone A causes increased transcription of AQP2 after 4 hours. In cells pretreated with a PKA inhibitor, V no longer increases membrane AQP2. In cells pretreated with a transcription inhibitor, A no longer increases total AQP2 protein after 4 hours.
Which comparative conclusion is most consistent with these findings?
Answer: V primarily triggers rapid trafficking via a second-messenger kinase pathway, whereas A primarily alters gene expression via a slower transcription-dependent mechanism
This question tests understanding of distinct hormone signal transduction mechanisms - rapid protein trafficking versus slower transcriptional regulation - in controlling the same target protein (AQP2). Signal transduction can achieve similar endpoints through different mechanisms: rapid responses often involve post-translational modifications and protein trafficking, while slower responses typically require gene transcription and protein synthesis. Hormone V's rapid effect (10 minutes) blocked by PKA inhibition indicates a cAMP-PKA pathway triggering vesicle fusion to insert pre-existing AQP2 into membranes, while hormone A's slow effect (4 hours) blocked by transcription inhibition indicates genomic regulation increasing AQP2 synthesis. Option B correctly captures this distinction between rapid trafficking and slow transcriptional mechanisms. The distractor A incorrectly assigns intracellular receptor signaling to the rapid response, while C wrongly suggests both require protein synthesis for the 10-minute effect. When comparing hormone mechanisms, use response timing as a key discriminator: minutes suggest post-translational regulation, while hours indicate transcriptional changes.
- A cytokine (C) binds a cell-surface receptor that lacks intrinsic kinase activity but associates with a cytosolic tyrosine kinase. Upon C binding, the associated kinase phosphorylates the receptor, creating docking sites for transcription factors that are then phosphorylated and translocate to the nucleus. In a drug screen, compound X prevents nuclear accumulation of the transcription factor without affecting C binding to the receptor or receptor surface expression.
Based on the scenario, which step is most likely to be influenced by compound X?
Answer: Activation of the receptor-associated cytosolic tyrosine kinase or its ability to phosphorylate targets
This question tests understanding of cytokine receptor signal transduction through receptor-associated tyrosine kinases, specifically the JAK-STAT pathway where receptors lacking intrinsic kinase activity recruit cytosolic kinases for signaling. Cytokine receptors often lack intrinsic kinase domains but associate with cytosolic tyrosine kinases like JAKs, which phosphorylate the receptor upon ligand binding to create docking sites for transcription factors like STATs that are then phosphorylated and translocate to the nucleus. In this scenario, compound X prevents nuclear accumulation of the transcription factor without affecting cytokine binding or receptor expression, suggesting it interferes with the kinase activity or phosphorylation events downstream of receptor binding. The correct answer B identifies that compound X most likely influences the activation of the receptor-associated cytosolic tyrosine kinase or its ability to phosphorylate targets, as this is the critical step between receptor binding and transcription factor activation. A common distractor (D) incorrectly suggests the receptor has an intrinsic RTK domain, when the question explicitly states it lacks intrinsic kinase activity and uses an associated kinase. When analyzing cytokine receptor signaling, remember that many cytokine receptors depend on recruited kinases rather than intrinsic kinase domains, making the activation and function of these associated kinases a key regulatory point in the pathway.
- In a neuronal cell model, a ligand (N) binds a ligand-gated ion channel that is permeable to Na+. Channel opening depolarizes the membrane and triggers voltage-gated Ca2+ channel opening, increasing intracellular Ca2+. A separate ligand (M) binds a GPCR coupled to Gq, activating phospholipase C (PLC) and generating IP3, which releases Ca2+ from the endoplasmic reticulum. Both ligands can elevate cytosolic Ca2+, but by distinct mechanisms.
Which outcome would be expected if extracellular Na+ is removed while N is applied, with all other conditions unchanged?
Answer: Reduced depolarization and reduced Ca2+ influx through voltage-gated Ca2+ channels
This question tests understanding of ligand-gated ion channel signaling and the role of ion gradients in generating membrane depolarization that triggers voltage-gated calcium channel opening. Ligand-gated sodium channels depend on the electrochemical gradient for Na+ to produce inward current and membrane depolarization when opened, which then activates voltage-gated calcium channels as a secondary response. In this scenario, removing extracellular Na+ eliminates the driving force for Na+ entry through the ligand-gated channel when N binds, preventing the depolarization needed to open voltage-gated Ca2+ channels. The correct answer B accurately predicts reduced depolarization and reduced Ca2+ influx through voltage-gated channels, because the initial Na+-dependent depolarization is blocked. A common distractor (A) incorrectly suggests that N directly generates IP3, confusing the ligand-gated channel mechanism with GPCR-PLC signaling like that used by ligand M. When analyzing ion channel signaling cascades, trace the sequence of events from initial ion flux through secondary voltage-dependent responses, recognizing that removing the permeant ion eliminates the primary signal that triggers downstream events. - A lipid-soluble hormone (H) in plasma was measured at a constant total concentration before and after an acute decrease in its carrier protein (CBP) concentration. Shortly after CBP reduction, target cells showed increased expression of an H-responsive gene. Which outcome would be expected immediately after CBP decreases, assuming total H remains constant?
Answer: Increased free H fraction, increasing diffusion into cells and receptor activation
This question tests hormone transport, receptors, and signal transduction, exploring carrier protein effects on lipid-soluble hormones. Signal transduction for such hormones involves free fraction diffusion to intracellular receptors for gene expression. Reducing CBP increases free H, enhancing cellular entry and activation. Choice B logically follows, with more free H driving expression despite constant total. Choice A reverses the effect, a common equilibrium misunderstanding. In analogous problems, recall bound versus free dynamics. Assess immediate versus long-term transport changes.
- A GPCR agonist (Ag) increased cellular cAMP in a dose-dependent manner. When cells were pretreated with a toxin that ADP-ribosylates Gαs and prevents GTP hydrolysis, Ag produced a larger and more prolonged cAMP signal. Which cellular response is most consistent with the mechanism of the toxin?
Answer: Prolonged adenylyl cyclase activation due to sustained active Gαs-GTP
This question evaluates hormone transport, receptors, and signal transduction, focusing on G protein modifications in cAMP signaling. Signal transduction involves Gα GTPase cycle, with hydrolysis terminating activation. The toxin locks Gαs in active GTP form, prolonging cyclase stimulation. Choice B matches the sustained active Gαs-GTP causing prolonged cAMP. Choice A distracts with binding loss, but toxin affects hydrolysis. In similar scenarios, recall toxin mechanisms like cholera. Analyze signal duration for regulatory insights. - In cardiomyocytes, a hormone (E) increases contractility within seconds. E binds a cell-surface receptor; downstream, intracellular Ca2+ rises and phosphorylation of L-type calcium channels increases. When cells are pretreated with a Gs inhibitor, E no longer increases channel phosphorylation. When cells are pretreated with an inhibitor of phospholipase C (PLC), E still increases channel phosphorylation.
Which cellular response is most consistent with the signal transduction pathway described?
Answer: Increased phosphorylation of membrane proteins by PKA due to Gs-dependent cAMP production
This question tests understanding of G protein-coupled receptor signal transduction, specifically distinguishing between Gs-mediated cAMP/PKA pathways and Gq-mediated PLC/IP3 pathways in hormone signaling. Signal transduction through GPCRs involves specific G protein subtypes: Gs stimulates adenylyl cyclase to produce cAMP and activate PKA, while Gq activates PLC to generate IP3 and DAG. The experimental evidence shows hormone E requires Gs (blocked by Gs inhibitor) but not PLC (still works with PLC inhibitor) for channel phosphorylation, indicating option A is correct - E signals through Gs to produce cAMP and activate PKA. The rapid timeframe (seconds) and phosphorylation outcome are consistent with PKA-mediated effects on ion channels. Common distractors like option C incorrectly emphasize the IP3 pathway despite the PLC inhibitor having no effect, while option D suggests RTK signaling inconsistent with GPCR/G protein involvement. When analyzing GPCR questions, use specific inhibitor effects to map the pathway: Gs inhibition blocking the response indicates cAMP/PKA involvement, while PLC inhibition having no effect rules out the IP3/Ca2+ branch. - In cultured ovarian granulosa cells, follicle-stimulating hormone (FSH) increased aromatase expression over several hours. Early after stimulation, cAMP rose and a transcription factor became phosphorylated. If the FSH receptor is blocked, which outcome would be expected?
Answer: Reduced cAMP signaling and reduced induction of aromatase expression
This question tests hormone transport, receptors, and signal transduction, examining FSH's cAMP-mediated effects in ovarian cells. Signal transduction involves GPCR activation increasing cAMP for transcription factor phosphorylation and gene expression. FSH binds receptors, elevating cAMP to induce aromatase. Blockade reduces cAMP and expression, as in choice A. Choice B suggests feedback prevention, but blockade halts activation. In like questions, link messengers to transcriptional outcomes. Assess timing for second-messenger versus gene changes.
- In thyroid follicular cells, investigators track transport of two hormones: TSH (a glycoprotein peptide) and T3 (a thyroid hormone). In serum-like medium containing albumin, T3 is mostly protein-bound, whereas TSH remains largely unbound. Cells are exposed to equal total concentrations of TSH and T3. TSH produces a rapid increase in intracellular cAMP, while T3 produces no immediate change in cAMP but increases transcription of a metabolic gene after several hours.
Which statement best accounts for these observations?
Answer: TSH signals through a membrane receptor coupled to cAMP, whereas T3 enters cells and alters gene transcription via an intracellular receptor
This question tests understanding of peptide versus steroid hormone transport, receptor localization, and distinct signal transduction mechanisms. Signal transduction pathways fundamentally differ based on hormone hydrophobicity: hydrophilic peptides like TSH cannot cross membranes and must bind cell-surface receptors, while lipophilic hormones like T3 diffuse across membranes to bind intracellular receptors. The experimental observations - TSH causing rapid cAMP increase and T3 causing delayed transcriptional changes - perfectly match option C's explanation of TSH using membrane receptor-cAMP signaling while T3 enters cells for genomic effects. The albumin binding detail is a distractor element, as it affects free hormone concentration but doesn't change the fundamental signaling mechanisms. Common mistakes include option B suggesting T3 uses a GPCR (contradicted by no cAMP response) or option D proposing both use RTKs (inconsistent with the cAMP data). When analyzing hormone comparisons, use the response timing (seconds/minutes vs. hours) and second messenger involvement (cAMP presence/absence) to distinguish between membrane receptor signaling and genomic pathways.
- A β-adrenergic agonist is applied to isolated cardiac myocytes for 5 minutes. The receptor couples to Gs, leading to activation of adenylyl cyclase and increased cAMP. Protein kinase A (PKA) activity rises, and phosphorylation of a Ca2+-handling protein increases. In a separate dish, cells are treated with a membrane-permeable inhibitor that specifically blocks PKA catalytic activity but does not affect cAMP production.
Which cellular response is most consistent with the signal transduction pathway described when PKA is inhibited?
Answer: Reduced phosphorylation of the Ca2+-handling protein despite elevated cAMP levels
This question tests understanding of β-adrenergic receptor signal transduction through the Gs-cAMP-PKA pathway and the role of PKA in phosphorylating downstream targets. β-adrenergic receptors are GPCRs that couple to Gs proteins, which activate adenylyl cyclase to produce cAMP, leading to PKA activation and subsequent phosphorylation of target proteins like Ca2+-handling proteins in cardiac myocytes. In this scenario, when PKA is specifically inhibited while cAMP production continues normally, the phosphorylation of Ca2+-handling proteins would be reduced despite elevated cAMP levels. The correct answer C accurately reflects that PKA is the kinase responsible for phosphorylating these targets, so blocking PKA prevents phosphorylation even when cAMP is high. A common distractor (D) incorrectly suggests that cAMP directly phosphorylates proteins, when in fact cAMP acts by activating PKA, which then performs the phosphorylation. When analyzing GPCR signaling cascades, remember that second messengers like cAMP activate specific kinases (PKA) that carry out the actual phosphorylation events, creating a clear hierarchy in the signal transduction pathway. - A cultured thyroid follicular cell line was treated with thyroid-stimulating hormone (TSH). Within 2 minutes, intracellular cAMP increased; within 10 minutes, iodide uptake increased. A mutant receptor (R*) bound TSH normally but failed to increase cAMP. Which step is most likely impaired in cells expressing R*?
Answer: Activation of a heterotrimeric G protein that stimulates adenylyl cyclase
This question assesses hormone transport, receptors, and signal transduction, particularly TSH signaling in thyroid cells via cAMP-mediated pathways. Signal transduction involves receptor-ligand interaction activating G proteins to stimulate adenylyl cyclase and elevate cAMP for downstream effects. In this case, TSH binds its GPCR, activating Gs to increase cAMP and enhance iodide uptake. The mutant receptor impairs G protein activation, preventing cAMP rise despite binding, as in choice B. A distractor such as choice C might confuse TSH with steroid mechanisms, but TSH does not diffuse intracellularly. For related questions, identify if the receptor is a GPCR by second-messenger involvement. Verify pathway steps by noting timing and mutant effects.
