Signal Transduction Practice Questions

Q: Which of the following binds to a Tyrosine Kinase receptor?

Insulin. **Explanation:** The correct answer is **Insulin**. Insulin acts through a **Receptor Tyrosine Kinase (RTK)**, which is a transmembrane protein with intrinsic enzymatic activity. Upon insulin binding, the receptor undergoes autophosphorylation on tyrosine residues, which then triggers a signaling cascade involving Insulin Receptor Substrates (IRS-1/2) and the PI3K/Akt pathway. This is a high-yield concept as it distinguishes metabolic hormones from those using secondary messengers. **Analysis of Incorrect Options:** * **Luteinizing Hormone (LH) & Thyroid-Stimulating Hormone (TSH):** Both are glycoprotein hormones that bind to **G-Protein Coupled Receptors (GPCRs)**. Specifically, they activate the **Gs-adenylyl cyclase-cAMP** pathway. * **Thyrotropin-Releasing Hormone (TRH):** This hypothalamic hormone also binds to a **GPCR**, but it utilizes the **Gq-phospholipase C (PLC)** pathway, leading to an increase in Inositol triphosphate (IP3) and Diacylglycerol (DAG). **High-Yield Clinical Pearls for NEET-PG:** * **Mnemonic for RTK:** "The **PIG** **G**rows **F**ast" (**P**rolactin*, **I**nsulin, **G**rowth Hormone*, **G**rowth **F**actors like EGF, PDGF). * *Note: GH and Prolactin use JAK-STAT (Receptor-associated Tyrosine Kinase), while Insulin and EGF use Intrinsic Tyrosine Kinase.* * **Insulin Receptor Structure:** It is a heterotetramer ($\alpha_2\beta_2$). The $\alpha$-subunits are extracellular (binding site), and the $\beta$-subunits are transmembrane (catalytic site). * **GLUT4:** The PI3K pathway activated by the insulin receptor is responsible for the translocation of GLUT4 to the cell membrane in muscle and adipose tissue.

Q: Which receptor has intrinsic enzymatic activity?

Insulin receptor. ### Explanation **1. Why Insulin Receptor is Correct:** The **Insulin receptor** is a classic example of a **Receptor Tyrosine Kinase (RTK)**. These are transmembrane proteins that possess **intrinsic enzymatic activity**. Upon binding of insulin to the extracellular $\alpha$-subunits, a conformational change occurs in the intracellular $\beta$-subunits. This triggers **autophosphorylation** of tyrosine residues, which then activates downstream signaling molecules like Insulin Receptor Substrate (IRS-1), leading to the metabolic effects of insulin. **2. Why Other Options are Incorrect:** * **Progesterone Receptor (Option B):** This is a **Nuclear Receptor**. Progesterone is a steroid hormone that is lipophilic; it crosses the cell membrane and binds to receptors in the cytoplasm or nucleus, which then act as ligand-activated transcription factors. * **Thyroxine Receptor (Option C):** This is also a **Nuclear Receptor**. Thyroid hormones (T3/T4) bind to receptors already located on the DNA in the nucleus to regulate gene expression. * **Glucagon Receptor (Option D):** This is a **G-Protein Coupled Receptor (GPCR)**. It does *not* have intrinsic enzymatic activity. Instead, it activates an intermediary membrane-bound enzyme, **Adenylate Cyclase**, via a Gs-protein to produce the second messenger cAMP. **3. Clinical Pearls & High-Yield Facts for NEET-PG:** * **Other RTKs:** Receptors for IGF-1, EGF, PDGF, and FGF also possess intrinsic tyrosine kinase activity. * **JAK-STAT Pathway:** Receptors for Growth Hormone and Prolactin do **not** have intrinsic activity; they recruit soluble kinases (Janus Kinase) to signal. * **Insulin Resistance:** Often involves defects in the post-receptor signaling pathway (e.g., serine phosphorylation of IRS-1 instead of tyrosine phosphorylation). * **Mnemonic:** "Intrinsic" = Insulin, IGF, Growth Factors (except GH).

Q: Which specific enzyme inactivates cyclic AMP?

Phosphodiesterase. **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.

Q: Phospholipase C acts as a secondary messenger for which of the following hormones?

Gonadotropin-Releasing Hormone (GnRH). **Explanation:** The correct answer is **Gonadotropin-Releasing Hormone (GnRH)**. Hormones act via specific signal transduction pathways. GnRH binds to G-protein coupled receptors (GPCRs) linked to the **Gq protein**. This activates the enzyme **Phospholipase C (PLC)**, which cleaves phosphatidylinositol 4,5-bisphosphate (PIP2) into two secondary messengers: **Inositol triphosphate (IP3)** and **Diacylglycerol (DAG)**. IP3 triggers the release of calcium from the endoplasmic reticulum, while DAG activates Protein Kinase C (PKC), leading to the secretion of LH and FSH. **Analysis of Incorrect Options:** * **FSH and TSH:** These are glycoprotein hormones that act via the **Gs protein-cAMP pathway**. Binding to their receptors activates Adenylyl Cyclase, which increases intracellular cAMP levels. * **Inhibin:** This is a member of the TGF-β superfamily. It acts through **Serine/Threonine kinase receptors** and the **SMAD** signaling pathway, rather than the PLC or cAMP systems. **High-Yield Clinical Pearls for NEET-PG:** * **Gq-PLC Pathway Mnemonic:** Remember **"GOAT HAG"** for hormones using the PLC/IP3 pathway: **G**nRH, **O**xytocin, **A**DH (V1 receptor), **T**RH, **H**istamine (H1), **A**ngiotensin II, and **G**astrin. * **Pulsatility:** GnRH must be secreted in a pulsatile manner to maintain receptor sensitivity. Continuous administration leads to "downregulation" of receptors, a principle used clinically in treating prostate cancer and endometriosis (GnRH analogues). * **V1 vs. V2:** ADH uses the PLC pathway for vasoconstriction (V1 receptor) but the cAMP pathway for water reabsorption in the kidney (V2 receptor).

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

ADP ribosylation. **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**.

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

Transcription factor. **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.

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

Growth hormone. 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**.

Q: Which of the following is NOT true about G proteins?

G proteins are made up of 4 subunits.. **Explanation:** **Why Option C is correct:** G proteins (Guanine nucleotide-binding proteins) are **heterotrimeric**, meaning they are composed of **three subunits**: **Alpha (α), Beta (β), and Gamma (γ)** [1]. They are not made of 4 subunits. In the inactive state, the α-subunit binds GDP [2]. Upon ligand binding to a G-protein coupled receptor (GPCR), GDP is replaced by GTP, causing the α-subunit to dissociate from the βγ-complex to trigger downstream signaling [3]. **Analysis of other options:** * **Option A:** G proteins directly or indirectly regulate various ion channels (e.g., K+ channels in the heart via G_i), often referred to as G-protein-gated ion channels [3]. * **Option B:** G proteins (specifically G_s) activate Adenylyl Cyclase, increasing cAMP [4]. This activates Protein Kinase A, which phosphorylates **Phosphorylase Kinase**, leading to the formation of **Active Glycogen Phosphorylase** [4]. * **Option D:** The **Ras protein** is a member of the "Small GTPase" superfamily. These are "monomeric" G proteins (single subunit) that function similarly to the α-subunit of heterotrimeric G proteins and are critical in cell growth signaling; mutations in Ras are linked to various cancers [1]. **High-Yield Clinical Pearls for NEET-PG:** * **Vibrio cholerae toxin:** Causes ADP-ribosylation of **G_s**, locking it in the "ON" state (persistent high cAMP) [5]. * **Bordetella pertussis toxin:** Causes ADP-ribosylation of **G_i**, locking it in the "OFF" state (preventing inhibition of cAMP) [5]. * **Second Messengers:** G_s and G_i act on Adenylyl Cyclase (cAMP), while **G_q** acts on Phospholipase C (IP3/DAG/Ca2+).

Question 1

Which of the following binds to a Tyrosine Kinase receptor?

Accepted Answer

Insulin

Answer

Luteinizing Hormone (LH)

Answer

Thyroid-Stimulating Hormone (TSH)

Answer

Thyrotropin-Releasing Hormone (TRH)

Question 2

Which receptor has intrinsic enzymatic activity?

Accepted Answer

Insulin receptor

Answer

Progesterone receptor

Answer

Thyroxine receptor

Answer

Glucagon receptor

Question 3

Members of the multi-pass, G protein-linked family of receptors include the muscarinic cholinergic and $\beta$-adrenergic receptors and rhodopsin. Which of the following characterizes these receptors?

Accepted Answer

They can activate plasma membrane-bound enzymes or ion channels.

Answer

They possess a single hydrophobic transmembrane segment in the form of an alpha helix.

Answer

They possess an intracellular ligand-binding domain.

Answer

They possess intrinsic enzyme activity.

Question 4

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

Accepted Answer

Phosphorylation of an importin protein increases its binding affinity for transcription factors.

Answer

Detachment of the transcription factor from a complexing protein can unmask a nuclear localization signal.

Answer

Phosphorylation of the transcription factor can increase its importin binding affinity.

Answer

Dephosphorylation of the transcription factor can increase its importin binding affinity.

Question 5

Which specific enzyme inactivates cyclic AMP?

Accepted Answer

Phosphodiesterase

Answer

Phosphate

Answer

Protein kinase

Answer

Adenyl cyclase

Question 6

Phospholipase C acts as a secondary messenger for which of the following hormones?

Accepted Answer

Gonadotropin-Releasing Hormone (GnRH)

Answer

Follicle-Stimulating Hormone (FSH)

Answer

Inhibin

Answer

Thyroid-Stimulating Hormone (TSH)

Question 7

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

Accepted Answer

ADP ribosylation

Answer

ATP-ADP transfer

Answer

Phosphorylation

Answer

Dephosphorylation

Question 8

Activation of G-protein regulates all of the following except?

Accepted Answer

Transcription factor

Answer

Adenyl cyclase activity

Answer

Ion channels

Answer

IP3 & DAG

Question 9

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

Accepted Answer

Growth hormone

Answer

Thyroid hormone

Answer

Insulin

Answer

Glucocorticoids

Question 10

Which of the following is NOT true about G proteins?

Accepted Answer

G proteins are made up of 4 subunits.

Answer

G channels are regulated by G proteins.

Answer

G proteins are involved in phosphorylase formation.

Answer

G proteins are related to the Ras oncogene.

Signal Transduction — MCQs

Signal Transduction — MCQs

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