Signal Transduction — MCQs

Signal Transduction Indian Medical PG Practice Questions and MCQs

Question 61: Signal pathways activate transcription factors for their transport into the nucleus by all mechanisms EXCEPT:

A. Detachment of the transcription factor from a complexing protein can unmask a nuclear localization signal.
B. Phosphorylation of an importin protein increases its binding affinity for transcription factors. (Correct Answer)
C. Phosphorylation of the transcription factor can increase its importin binding affinity.
D. Dephosphorylation of the transcription factor can increase its importin binding affinity.

Explanation: ### Explanation The transport of transcription factors (TFs) from the cytoplasm to the nucleus is a highly regulated process, typically mediated by **Importins**. These carrier proteins recognize specific amino acid sequences on the TF called **Nuclear Localization Signals (NLS)**. **Why Option B is the Correct Answer (The "Except"):** The regulation of nuclear import occurs by modifying the **Transcription Factor (cargo)** or its **anchoring proteins**, not by phosphorylating the importin itself. Importins (like Importin-α and β) have a constitutive affinity for NLS sequences; their binding capacity is regulated by the concentration of **Ran-GTP** in the nucleus, which triggers cargo release, rather than phosphorylation of the importin protein to increase binding. **Analysis of Other Options:** * **Option A:** Many TFs are held in the cytoplasm by inhibitory proteins (e.g., **IκB** holds **NF-κB**). Upon signaling, the inhibitor dissociates, unmasking the NLS and allowing transport. * **Option C:** Phosphorylation can induce a conformational change in a TF that exposes a hidden NLS or directly increases its affinity for importins (e.g., **STAT** proteins require phosphorylation for dimerization and entry). * **Option D:** Conversely, some TFs require dephosphorylation to enter the nucleus. A classic example is **NFAT** (Nuclear Factor of Activated T-cells), which is dephosphorylated by **Calcineurin** to expose its NLS. **High-Yield Clinical Pearls for NEET-PG:** * **NF-κB Pathway:** Pro-inflammatory signals lead to the phosphorylation and degradation of **IκB**, allowing NF-κB to enter the nucleus. * **Steroid Receptors:** These are TFs that often reside in the cytoplasm bound to **Heat Shock Proteins (HSPs)**. Ligand binding causes detachment from HSPs (Option A mechanism). * **Ran-GTPase:** This molecular switch provides directionality; **Ran-GTP** is high in the nucleus (promotes cargo release), while **Ran-GDP** is high in the cytoplasm.

Question 62: Which specific enzyme inactivates cyclic AMP?

A. Phosphodiesterase (Correct Answer)
B. Phosphate
C. Protein kinase
D. Adenyl cyclase

Explanation: **Explanation:** **1. Why Phosphodiesterase (PDE) is correct:** Cyclic AMP (cAMP) acts as a vital second messenger in signal transduction pathways (e.g., G-protein coupled receptors). To terminate the signal and prevent overstimulation, cAMP must be inactivated. The enzyme **Phosphodiesterase** catalyzes the hydrolysis of the 3',5'-phosphodiester bond in cAMP, converting it into **5'-AMP**, which is biologically inactive in the signaling cascade. **2. Analysis of Incorrect Options:** * **Phosphate (B):** This is an inorganic ion, not an enzyme. While phosphorylation/dephosphorylation (via kinases/phosphatases) regulates protein activity, it does not degrade the cAMP molecule itself. * **Protein Kinase (C):** Specifically Protein Kinase A (PKA), is the *target* activated by cAMP. It propagates the signal by phosphorylating downstream proteins; it does not inactivate cAMP. * **Adenyl Cyclase (D):** This enzyme is responsible for the **synthesis** of cAMP from ATP, acting as the "on-switch" rather than the "off-switch." **3. Clinical Pearls & High-Yield Facts for NEET-PG:** * **PDE Inhibitors:** Several drugs work by inhibiting this enzyme to keep cAMP levels high. Examples include **Theophylline** (bronchodilation in asthma), **Milrinone** (inotropic support in heart failure), and **Sildenafil** (inhibits PDE-5 to treat erectile dysfunction). * **Caffeine:** Acts as a non-specific phosphodiesterase inhibitor, leading to prolonged cAMP activity and its characteristic stimulatory effects. * **Cholera Toxin:** Increases cAMP by permanently activating Adenyl Cyclase, leading to severe diarrhea.

Question 63: IGF-1 acts through which of the following receptors?

A. Cytokine related receptor
B. G protein coupled receptor
C. Tyrosine kinase receptor (Correct Answer)
D. Nuclear or cytoplasmic receptor

Explanation: **Explanation:** **1. Why Option C is Correct:** Insulin-like Growth Factor-1 (IGF-1) acts via the **IGF-1 receptor (IGF-1R)**, which belongs to the **Receptor Tyrosine Kinase (RTK)** family. Structurally, it is a heterotetramer (2α and 2β subunits) very similar to the Insulin receptor. Upon binding of IGF-1 to the extracellular α-subunits, the intracellular β-subunits undergo **autophosphorylation** of tyrosine residues. This triggers downstream signaling pathways, primarily the **PI3K/Akt** pathway (mediating cell survival and growth) and the **MAPK/ERK** pathway (mediating cell proliferation). **2. Why Other Options are Incorrect:** * **Option A (Cytokine-related receptor):** These receptors (e.g., GH, Prolactin, Erythropoietin) lack intrinsic kinase activity and instead signal through recruited **JAK-STAT** pathways. While Growth Hormone (GH) stimulates the production of IGF-1 via this mechanism, IGF-1 itself uses an RTK. * **Option B (GPCR):** G-protein coupled receptors use second messengers like cAMP or IP3/DAG. Examples include Glucagon, PTH, and ACTH. * **Option D (Nuclear/Cytoplasmic receptor):** These are used by lipid-soluble hormones like Steroids, Thyroid hormones, and Vitamin D, which act as transcription factors. IGF-1 is a peptide hormone and cannot cross the cell membrane. **3. High-Yield Clinical Pearls for NEET-PG:** * **The "Insulin-Like" Connection:** Both Insulin and IGF-1 use Tyrosine Kinase receptors. * **Laron Dwarfism:** Caused by a mutation in the **GH receptor** (JAK-STAT type), leading to low levels of IGF-1 despite high GH levels. * **Acromegaly Diagnosis:** Serum **IGF-1 levels** are the best screening test for Acromegaly because they remain stable throughout the day, unlike pulsatile GH levels. * **Key RTK Ligands:** Remember the mnemonic **"PIG"** — **P**latelet-derived growth factor, **I**nsulin/IGF-1, and **G**rowth factors (EGF, VEGF).

Question 64: Which of the following is a drug that acts on a tyrosine kinase receptor?

A. Thyrotropin-releasing hormone (TRH)
B. Thyroid-stimulating hormone (TSH)
C. Insulin (Correct Answer)
D. Melanocyte-stimulating hormone (MSH)

Explanation: **Explanation:** **1. Why Insulin is Correct:** Insulin acts through a **Receptor Tyrosine Kinase (RTK)**, which is a transmembrane protein with intrinsic enzymatic activity. The insulin receptor is a heterotetramer ($\alpha_2\beta_2$). When insulin binds to the extracellular $\alpha$-subunits, it triggers **autophosphorylation** of tyrosine residues on the intracellular $\beta$-subunits. This creates docking sites for **Insulin Receptor Substrates (IRS-1/2)**, initiating downstream signaling pathways like the PI3K/Akt pathway (mediating metabolic effects like glucose uptake via GLUT4) and the MAPK pathway (mediating growth and gene expression). **2. Why the Other Options are Incorrect:** * **TRH (Option A):** Acts via the **Gq protein-coupled receptor (GPCR)** pathway, activating Phospholipase C (PLC) to increase IP3 and DAG levels. * **TSH (Option B):** Acts via the **Gs protein-coupled receptor** pathway, activating Adenylyl Cyclase to increase intracellular cAMP. * **MSH (Option D):** Also acts via the **Gs-cAMP pathway** (specifically through Melanocortin receptors). **3. NEET-PG High-Yield Clinical Pearls:** * **Intrinsic Tyrosine Kinase:** Includes Insulin, IGF-1, EGF, PDGF, and FGF. * **JAK-STAT Pathway (Non-intrinsic Tyrosine Kinase):** Used by Growth Hormone, Prolactin, Erythropoietin, and Leptin. Remember: "PIGGLy" (Prolactin, Immunomodulators/Cytokines, GH, G-CSF, Leptin). * **cGMP Pathway:** Used by ANP, BNP, and Nitric Oxide. * **Zinc Finger Motif:** Common in receptors for steroid hormones, Thyroid hormone (T3/T4), and Vitamin D, which act directly on DNA.

Question 65: Which modification occurs in the Gs subunit, leading to watery diarrhea in cholera?

A. ADP ribosylation (Correct Answer)
B. ATP-ADP transfer
C. Phosphorylation
D. Dephosphorylation

Explanation: **Explanation:** The correct answer is **ADP ribosylation**. **Mechanism of Action:** Cholera toxin, produced by *Vibrio cholerae*, is an A-B type enterotoxin. The 'A' subunit possesses enzymatic activity; once inside the intestinal mucosal cell, it catalyzes the **ADP-ribosylation** of the **Gsα subunit** of the G-protein complex. This modification inhibits the intrinsic GTPase activity of the Gs subunit, locking it in a permanently "active" state. This leads to continuous stimulation of **Adenylate Cyclase**, resulting in high intracellular levels of **cAMP**. Elevated cAMP activates Protein Kinase A (PKA), which phosphorylates the **CFTR** (Cystic Fibrosis Transmembrane Conductance Regulator) chloride channels. This causes a massive efflux of chloride ions, followed by sodium and water, into the intestinal lumen, manifesting as "rice-water" diarrhea. **Analysis of Incorrect Options:** * **B. ATP-ADP transfer:** This is a general metabolic process (e.g., in glycolysis) and is not the mechanism of toxin-mediated G-protein modification. * **C & D. Phosphorylation/Dephosphorylation:** While these are common regulatory mechanisms for enzymes (via kinases and phosphatases), they are not the primary covalent modification induced by the cholera toxin. **High-Yield Clinical Pearls for NEET-PG:** * **Cholera Toxin:** ADP-ribosylates **Gs** (Stimulatory) → Permanent **ON** state. * **Pertussis Toxin:** ADP-ribosylates **Gi** (Inhibitory) → Permanent **OFF** state (prevents inhibition of Adenylate Cyclase, also increasing cAMP). * **Diphtheria Toxin:** ADP-ribosylates **EF-2** (Elongation Factor 2), inhibiting protein synthesis. * **Key Target:** The specific amino acid targeted by Cholera toxin for ADP-ribosylation is **Arginine**.

Question 66: Which of the following hormones utilizes cyclic GMP as a second messenger?

A. Growth hormone
B. Follicle-stimulating hormone (FSH)
C. Insulin (Correct Answer)
D. Thyroxin

Explanation: **Explanation:** The correct answer is **Insulin**. While insulin primarily acts through a **Tyrosine Kinase** receptor (MAPK and PI3K pathways), it also utilizes **cyclic GMP (cGMP)** as a second messenger for specific metabolic actions, such as the activation of phosphodiesterase to lower cAMP levels. In the context of NEET-PG, hormones using cGMP are often categorized into two groups: those acting via **Atrial Natriuretic Peptide (ANP/BNP)** receptors (membrane-bound guanylyl cyclase) and **Nitric Oxide (NO)** (soluble guanylyl cyclase). **Analysis of Options:** * **Growth Hormone (A):** Utilizes the **JAK-STAT** kinase pathway. It does not have intrinsic tyrosine kinase activity but recruits cytosolic kinases. * **FSH (B):** Like most pituitary gonadotropins (LH, TSH, hCG), FSH utilizes the **cAMP** second messenger system via Gs-protein coupled receptors. * **Thyroxin (D):** Being a lipid-soluble hormone, it acts through **nuclear receptors** to alter gene transcription directly; it does not use a second messenger system. **High-Yield Clinical Pearls for NEET-PG:** * **cGMP Mnemonics:** Remember **"V-A-I-N"** for cGMP: **V**asodilators (NO), **A**NP/BNP, **I**nsulin, and **N**itric Oxide. * **Tyrosine Kinase:** Insulin and IGF-1 have *intrinsic* tyrosine kinase activity, whereas GH and Prolactin *recruit* JAK-STAT. * **Sildenafil Connection:** Sildenafil (Viagra) works by inhibiting **Phosphodiesterase-5 (PDE-5)**, which normally breaks down cGMP, thereby prolonging vasodilation.

Question 67: Activation of G-protein regulates all of the following except?

A. Adenyl cyclase activity
B. Ion channels
C. IP3 & DAG
D. Transcription factor (Correct Answer)

Explanation: **Explanation:** The core concept here is the distinction between **G-Protein Coupled Receptors (GPCRs)**, which mediate rapid cellular responses via second messengers, and **Nuclear Receptors**, which directly regulate gene expression. **Why "Transcription Factor" is the correct answer:** G-proteins are membrane-associated proteins that act as molecular switches. While GPCR signaling can *eventually* lead to changes in gene expression (e.g., via the cAMP Response Element Binding protein - CREB), G-proteins do not **directly** activate or function as transcription factors. Transcription factors are typically regulated by lipid-soluble hormones (like steroids or thyroid hormones) that bind to intracellular receptors or via downstream kinase cascades (like the MAPK pathway). **Analysis of Incorrect Options:** * **Adenyl Cyclase (A):** This is a classic G-protein function. **Gs** stimulates and **Gi** inhibits Adenyl Cyclase, which converts ATP to cAMP. * **Ion Channels (B):** G-proteins can directly or indirectly regulate ion channels. For example, the **Gβγ subunit** of the Gi protein directly opens K+ channels (GIRK) in cardiac muscle, leading to hyperpolarization. * **IP3 & DAG (C):** The **Gq** protein activates Phospholipase C (PLC), which cleaves PIP2 into the second messengers Inositol triphosphate (IP3) and Diacylglycerol (DAG). **High-Yield Clinical Pearls for NEET-PG:** * **Cholera Toxin:** Inhibits GTPase activity of **Gs**, leading to permanent activation, high cAMP, and secretory diarrhea. * **Pertussis Toxin:** Inhibits **Gi**, preventing the inhibition of Adenyl Cyclase, leading to increased cAMP. * **G-protein structure:** They are heterotrimeric (α, β, γ subunits). The **α-subunit** has intrinsic GTPase activity, which acts as a "self-terminating" clock.

Question 68: Receptor for which of the following hormones is present intracellularly?

A. Insulin
B. Corticosteroid (Correct Answer)
C. Epinephrine
D. Glucagon

Explanation: **Explanation:** The location of a hormone receptor is primarily determined by the hormone's chemical nature (solubility). Hormones are classified into two main groups based on their signaling mechanism: 1. **Intracellular Receptors (Lipophilic Hormones):** These hormones are lipid-soluble and can easily cross the lipid bilayer of the plasma membrane. Their receptors are located in the **cytosol or nucleus**. * **Corticosteroids (Glucocorticoids/Mineralocorticoids)** are steroid hormones derived from cholesterol. Being lipophilic, they bind to intracellular receptors. Once bound, the hormone-receptor complex acts as a transcription factor, binding to Hormone Response Elements (HRE) on DNA to regulate gene expression. Other examples include Thyroid hormones (T3/T4), Vitamin D, Retinoic acid, and Sex steroids (Estrogen, Progesterone, Testosterone). 2. **Cell Surface Receptors (Hydrophilic Hormones):** These hormones are water-soluble and cannot cross the cell membrane. They bind to extracellular receptors, which then trigger second messenger systems. * **Insulin (Option A):** Binds to a transmembrane receptor with **Tyrosine Kinase** activity. * **Epinephrine (Option C) & Glucagon (Option D):** Both bind to **G-Protein Coupled Receptors (GPCR)**. Epinephrine acts via $\alpha$ and $\beta$ receptors, while Glucagon primarily utilizes the cAMP second messenger pathway. **High-Yield Clinical Pearls for NEET-PG:** * **Mnemonic for Intracellular Receptors:** "**VET TV**" (**V**itamin D, **E**strogen, **T**estosterone, **T**hyroid hormone, **V**itamin A/Retinoic acid) + **Corticosteroids**. * **Thyroid Hormone Exception:** Unlike most lipophilic hormones that bind in the cytosol, the Thyroid hormone receptor is always located **directly on the chromatin** in the nucleus. * **Speed of Action:** Hormones with intracellular receptors have a **slow onset** but **long duration** of action because they involve protein synthesis.

Question 69: Which of the following does not act as a second messenger?

A. Cyclic AMP
B. Inositol triphosphate
C. Diacylglycerol
D. G protein (Correct Answer)

Explanation: ### Explanation **1. Why G protein is the correct answer:** In signal transduction, **G proteins** (Guanine nucleotide-binding proteins) act as **transducers** or "molecular switches," not second messengers. They reside on the inner surface of the plasma membrane and relay the signal from the activated receptor (GPCR) to an effector enzyme (like Adenylyl cyclase or Phospholipase C). Second messengers are small, non-protein molecules that diffuse through the cytosol to amplify the signal; G proteins are large heterotrimeric membrane-bound proteins. **2. Why the other options are incorrect:** * **Cyclic AMP (cAMP):** The classic second messenger produced by Adenylyl cyclase. It primarily activates Protein Kinase A (PKA). * **Inositol triphosphate (IP3):** Produced by the cleavage of PIP2 by Phospholipase C. It binds to receptors on the Endoplasmic Reticulum to release **Calcium** (another vital second messenger) into the cytosol. * **Diacylglycerol (DAG):** Also produced from PIP2 cleavage. It remains membrane-bound and activates Protein Kinase C (PKC) in the presence of Calcium. **3. High-Yield Clinical Pearls for NEET-PG:** * **The "Big Five" Second Messengers:** cAMP, cGMP, IP3, DAG, and $Ca^{2+}$. * **G-protein subunits:** The **$\alpha$-subunit** possesses intrinsic GTPase activity, which acts as a self-limiting "off switch" by hydrolyzing GTP to GDP. * **Toxins:** *Vibrio cholerae* toxin inhibits the GTPase activity of $G_s$, leading to permanent activation of Adenylyl cyclase and massive cAMP-induced diarrhea. *Pertussis toxin* inhibits $G_i$, preventing the inhibition of Adenylyl cyclase. * **Nitric Oxide (NO):** Acts via **cGMP** to cause vasodilation (target of Sildenafil and Nitroglycerin).

Question 70: Which of the following hormones employs the JAK/STAT signalling cascade?

A. Growth hormone (Correct Answer)
B. Thyroid hormone
C. Insulin
D. Glucocorticoids

Explanation: The **JAK/STAT (Janus Kinase/Signal Transducer and Activator of Transcription)** pathway is a specialized signaling mechanism used primarily by cytokines and specific polypeptide hormones. ### 1. Why Growth Hormone is Correct **Growth Hormone (GH)** binds to a single-pass transmembrane receptor that lacks intrinsic enzymatic activity. Upon binding, the receptor recruits cytoplasmic **Janus Kinases (JAK2)**. These kinases cross-phosphorylate each other and the receptor, creating docking sites for **STAT proteins**. Once phosphorylated, STATs dimerize and translocate to the nucleus to act as transcription factors. Other hormones using this pathway include **Prolactin, Erythropoietin (EPO), and Leptin**. ### 2. Analysis of Incorrect Options * **Thyroid Hormone (B) & Glucocorticoids (D):** These are lipophilic hormones. They cross the cell membrane and bind to **Intracellular/Nuclear Receptors**, which act directly as ligand-regulated transcription factors. * **Insulin (C):** Insulin uses a **Receptor Tyrosine Kinase (RTK)**. Unlike JAK/STAT, the insulin receptor has *intrinsic* enzymatic activity in its intracellular domain, which phosphorylates Insulin Receptor Substrates (IRS) to activate the PI3K/AKT and MAPK pathways. ### 3. High-Yield Clinical Pearls for NEET-PG * **Mnemonic for JAK/STAT:** "PIGGLET" — **P**rolactin, **I**mmunomodulators (Cytokines/Interferons), **G**H, **G**-CSF, **L**eptin, **E**rythropoietin, **T**hrombopoietin. * **Clinical Correlation:** Mutations in **JAK2** (specifically V617F) are strongly associated with **Myeloproliferative Neoplasms** like Polycythemia Vera. * **Key Distinction:** If the receptor *has* intrinsic kinase activity, it is an **RTK** (e.g., Insulin, IGF-1). If it *recruits* a kinase, it is **JAK/STAT**.

Practice by Chapter

Cell Surface Receptors: Types and Functions

Practice Questions

G-Protein Coupled Receptors

Practice Questions

Enzyme-Linked Receptors

Practice Questions

Second Messengers in Signal Transduction

Practice Questions

cAMP and cGMP Signaling

Practice Questions

Calcium as Second Messenger

Practice Questions

Inositol Phosphate Pathway

Practice Questions

MAP Kinase Cascades

Practice Questions

JAK-STAT Signaling Pathway

Practice Questions

Insulin Signaling Pathway

Practice Questions

Nuclear Receptors and Gene Regulation

Practice Questions

Defects in Signal Transduction and Disease

Practice Questions

Want unlimited practice?

Get full access to all questions, explanations, and performance tracking.

Start For Free