Signal Transduction — MCQs

Signal Transduction Indian Medical PG Practice Questions and MCQs

Question 71: All of the following belong to the steroid receptor superfamily EXCEPT:

A. Vitamin D3 receptor
B. Thyroid receptor
C. Retinoid receptor
D. Epinephrine receptor (Correct Answer)

Explanation: **Explanation:** The **Steroid Receptor Superfamily** consists of intracellular receptors (located in the cytoplasm or nucleus) that act as **ligand-activated transcription factors**. These receptors share a common structural domain, including a highly conserved Zinc-finger DNA-binding domain. **Why Option D is Correct:** The **Epinephrine receptor** (Adrenergic receptor) is a **G-Protein Coupled Receptor (GPCR)**. Unlike steroid hormones, epinephrine is a catecholamine (water-soluble) that cannot cross the lipid bilayer. It binds to receptors on the **cell surface**, triggering a second messenger cascade (cAMP), rather than directly entering the nucleus to modulate transcription. **Why the other options are Incorrect:** * **Vitamin D3, Thyroid (T3/T4), and Retinoid (Vitamin A) receptors** all belong to the Type II subclass of the steroid receptor superfamily. * Despite their different chemical structures, these hormones are lipophilic and cross the plasma membrane to bind to receptors already located in the **nucleus**. * They typically form **heterodimers** with the Retinoid X Receptor (RXR) to bind to Hormone Response Elements (HRE) on DNA. **High-Yield Clinical Pearls for NEET-PG:** * **Location:** Steroid receptors (Estrogen, Progesterone, Glucocorticoids) are primarily cytoplasmic, while Thyroid and Retinoid receptors are always nuclear. * **Zinc Fingers:** The DNA-binding domain of this superfamily contains "Zinc Finger" motifs (Cys2-Cys2 type), a frequent target for MCQ questions. * **Mechanism:** They regulate gene expression by recruiting co-activators or co-repressors to the promoter region of target genes.

Question 72: Fibroblast Growth Factor mediates its effect through which of the following receptors?

A. Tyrosine kinase (Correct Answer)
B. cAMP
C. cGMP
D. Ca2+

Explanation: **Explanation:** **1. Why Tyrosine Kinase is Correct:** Fibroblast Growth Factor (FGF) belongs to a class of ligands that utilize **Receptor Tyrosine Kinases (RTKs)** for signal transduction. Upon FGF binding, the receptor undergoes dimerization, leading to the autophosphorylation of intracellular tyrosine residues. This triggers a downstream signaling cascade, most notably the **MAP Kinase (Ras-Raf-MEK-ERK) pathway**, which regulates cell proliferation, differentiation, and angiogenesis. Most growth factors (EGF, PDGF, IGF-1, Insulin) share this mechanism. **2. Why Other Options are Incorrect:** * **B. cAMP:** This is a second messenger for **G-Protein Coupled Receptors (GPCRs)** linked to Gs or Gi proteins. Hormones like Glucagon, ACTH, and PTH use this pathway, not growth factors. * **C. cGMP:** This pathway is utilized by **Atrial Natriuretic Peptide (ANP)** and **Nitric Oxide (NO)**. It involves guanylyl cyclase activation, leading to vasodilation and fluid balance regulation. * **D. Ca2+:** Calcium (and IP3/DAG) is the second messenger for GPCRs linked to the **Gq protein**. Examples include GnRH, Oxytocin, and Gastrin. **Clinical Pearls & High-Yield Facts for NEET-PG:** * **Achondroplasia:** Caused by a gain-of-function mutation in the **FGFR3** (FGF Receptor 3) gene, leading to inhibited bone growth. * **JAK-STAT Pathway:** Do not confuse RTKs with the JAK-STAT pathway. While both involve tyrosine phosphorylation, JAK-STAT is used by **Cytokines, Growth Hormone, and Prolactin** (receptors lack intrinsic kinase activity). * **SH2 Domains:** Proteins that bind to phosphorylated tyrosine residues on RTKs typically contain SH2 (Src Homology 2) domains.

Question 73: Adrenaline acts through which type of receptor?

A. Single pass receptor
B. Four pass receptor
C. Seven pass receptor (Correct Answer)
D. Ligand gated channel

Explanation: **Explanation:** **1. Why the Correct Answer is Right:** Adrenaline (Epinephrine) acts via **G-Protein Coupled Receptors (GPCRs)**, specifically the alpha (α) and beta (β) adrenergic receptors. These receptors are structurally characterized by a single polypeptide chain that traverses the plasma membrane **seven times**. Consequently, they are known as **Seven-pass receptors**, Hepthelical receptors, or Serpentine receptors. When adrenaline binds to the extracellular domain, it induces a conformational change that activates intracellular G-proteins ($G_s$, $G_i$, or $G_q$), leading to the production of second messengers like cAMP or $IP_3$/DAG. **2. Why the Other Options are Incorrect:** * **Option A (Single pass):** These are typically **Enzyme-linked receptors** (e.g., Insulin receptor, Growth Factor receptors like EGFR). They cross the membrane only once and often possess intrinsic tyrosine kinase activity. * **Option B (Four pass):** This structure is characteristic of certain **Ionotropic receptors** (e.g., Nicotinic Acetylcholine receptors, $GABA_A$ receptors), where four transmembrane segments form a subunit of an ion channel. * **Option D (Ligand-gated channel):** These are receptors that act as pores for ions (e.g., $Na^+$, $K^+$, $Cl^-$) upon ligand binding. Adrenaline does not directly open ion channels; it works through metabolic signaling (metabotropic). **3. Clinical Pearls & High-Yield Facts for NEET-PG:** * **Largest Receptor Family:** GPCRs are the largest family of cell surface receptors. * **Second Messengers:** * $\beta_1, \beta_2, \beta_3$ receptors act via **$G_s$** (Increases cAMP). * $\alpha_1$ receptors act via **$G_q$** (Increases $IP_3$/DAG/Calcium). * $\alpha_2$ receptors act via **$G_i$** (Decreases cAMP). * **Rhodopsin:** The photoreceptor in the retina is also a classic example of a seven-pass GPCR.

Question 74: Which of the following hormones are synthesized as peptide precursors?

A. Insulin
B. Parathyroid hormone (PTH)
C. Renin
D. All of the above (Correct Answer)

Explanation: **Explanation:** The synthesis of protein and peptide hormones follows a universal pathway: they are initially synthesized on ribosomes as large, inactive molecules called **Pre-prohormones**. These undergo post-translational modifications in the endoplasmic reticulum (removal of the signal peptide) to become **Prohormones**, and are further cleaved in the Golgi apparatus or secretory vesicles into the final active **Hormone**. * **Insulin (Option A):** Synthesized as *Preproinsulin*. The signal sequence is removed to form *Proinsulin*. In the secretory granules, Proinsulin is cleaved into active Insulin and C-peptide. * **Parathyroid Hormone (Option B):** Synthesized as *Prepro-PTH* (115 amino acids), which is cleaved to *Pro-PTH* (90 amino acids) and finally to the active PTH (84 amino acids). * **Renin (Option C):** Although often discussed as an enzyme, Renin is a peptide hormone synthesized as *Preprorenin*. It is processed into *Prorenin* and then into active Renin in the juxtaglomerular cells of the kidney. Since all three substances are peptide-based and follow this biosynthetic pathway, **Option D** is the correct answer. **High-Yield Clinical Pearls for NEET-PG:** * **C-Peptide:** Since C-peptide and Insulin are secreted in equimolar amounts from Proinsulin, C-peptide levels are used as a marker of endogenous insulin production (useful in distinguishing Type 1 vs. Type 2 Diabetes or Factitious Hypoglycemia). * **Storage:** Unlike steroid hormones (which are synthesized on demand), peptide hormones are stored in **secretory vesicles** and released via exocytosis in response to a stimulus (usually involving Calcium influx). * **Receptors:** Peptide hormones are water-soluble and cannot cross the lipid bilayer; they bind to **cell surface receptors** (GPCRs or Enzyme-linked receptors).

Question 75: Which of the following is NOT true about G proteins?

A. G channels are regulated by G proteins.
B. G proteins are involved in phosphorylase formation.
C. G proteins are made up of 4 subunits. (Correct Answer)
D. G proteins are related to the Ras oncogene.

Explanation: **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 76: Slow-reacting substance of anaphylaxis (SRS-A) is?

A. Prostaglandin
B. Leukotriene (Correct Answer)
C. Serotonin
D. Histamine

Explanation: **Explanation:** The correct answer is **Leukotriene**. **Slow-reacting substance of anaphylaxis (SRS-A)** is a mixture of specific cysteinyl leukotrienes, primarily **LTC4, LTD4, and LTE4**. These are synthesized via the **Lipoxygenase (LOX) pathway** from arachidonic acid. They are called "slow-reacting" because, unlike histamine which causes immediate bronchoconstriction, SRS-A induces a slower, more prolonged, and significantly more potent contraction of smooth muscle in the airways. **Why other options are incorrect:** * **Prostaglandins:** These are products of the Cyclooxygenase (COX) pathway. While they mediate inflammation and pain (e.g., PGD2 causes bronchoconstriction), they do not constitute SRS-A. * **Serotonin:** A monoamine neurotransmitter and vasoactive amine. While it plays a role in platelet aggregation and GI motility, it is not a component of SRS-A. * **Histamine:** This is a pre-formed mediator stored in mast cell granules. It is responsible for the **immediate** (Type I) hypersensitivity reaction but is rapidly metabolized, unlike the sustained action of SRS-A. **High-Yield Clinical Pearls for NEET-PG:** * **Potency:** Cysteinyl leukotrienes (SRS-A) are **100 to 1000 times more potent** than histamine in inducing bronchoconstriction and increasing vascular permeability. * **Aspirin-Exacerbated Respiratory Disease (AERD):** Inhibiting the COX pathway with Aspirin shunts arachidonic acid toward the LOX pathway, increasing leukotriene production and triggering asthma. * **Pharmacology Link:** **Montelukast and Zafirlukast** are leukotriene receptor antagonists (LTRA) used in chronic asthma management to block the effects of SRS-A. * **LTB4** is primarily involved in **chemotaxis** (neutrophil recruitment) and is not part of SRS-A.

Question 77: In the context of G-protein signaling, which of the following is considered a second messenger?

A. cAMP
B. Calcium (Correct Answer)
C. CO
D. NO

Explanation: **Explanation:** In G-protein coupled receptor (GPCR) signaling, **Calcium ($Ca^{2+}$)** is a classic second messenger. When a ligand binds to a $G_q$-coupled receptor, it activates Phospholipase C (PLC), which cleaves $PIP_2$ into $IP_3$ and DAG. $IP_3$ then binds to receptors on the endoplasmic reticulum, triggering the release of $Ca^{2+}$ into the cytosol. This rise in intracellular calcium activates various downstream proteins, such as Protein Kinase C (PKC) and Calmodulin. **Analysis of Options:** * **A. cAMP:** While cAMP is a major second messenger (produced via $G_s$ signaling), it is often categorized alongside $Ca^{2+}$. However, in the context of specific exam questions where multiple options might seem correct, $Ca^{2+}$ is frequently highlighted for its unique role in the $IP_3/DAG$ pathway. *Note: If this were a "multiple correct" format, both A and B would be right; however, in single-best-answer formats, $Ca^{2+}$ is a high-yield focus for $G_q$ pathways.* * **C & D. CO and NO:** Carbon Monoxide (CO) and Nitric Oxide (NO) are categorized as **gasotransmitters** or "third messengers." They are paracrine signaling molecules that can diffuse across membranes to activate intracellular targets (like guanylyl cyclase), rather than being traditional second messengers generated directly by GPCR activation. **High-Yield Clinical Pearls for NEET-PG:** * **$G_q$ Pathway:** Remember the mnemonic **"HAV 1 M&M"** (Histamine-$H_1$, Adrenergic-$\alpha_1$, Vasopressin-$V_1$, Muscarinic-$M_1$ and $M_3$)—all use the $IP_3/Ca^{2+}$ second messenger system. * **Calmodulin:** Calcium often acts by binding to Calmodulin; this complex then activates Myosin Light Chain Kinase (MLCK), essential for smooth muscle contraction. * **Amplification:** The primary purpose of second messengers is the intracellular amplification of the extracellular signal.

Question 78: Insulin receptors are:

A. Tyrosine Kinase receptors (Correct Answer)
B. Phosphodiesterase
C. Calcium calmodulin
D. Lipoprotein

Explanation: **Explanation:** **1. Why Tyrosine Kinase Receptors is correct:** The insulin receptor is a classic example of a **Receptor Tyrosine Kinase (RTK)**. It is a heterotetrameric glycoprotein consisting of two extracellular $\alpha$-subunits (which bind insulin) and two transmembrane $\beta$-subunits. Upon insulin binding, the $\beta$-subunits undergo **autophosphorylation** on tyrosine residues. This triggers a signaling cascade by recruiting **Insulin Receptor Substrates (IRS 1-4)**, which subsequently activate the PI3K (Phosphoinositide 3-kinase) pathway for metabolic effects (like GLUT4 translocation) and the MAPK pathway for growth and gene expression. **2. Why other options are incorrect:** * **Phosphodiesterase (B):** This is an enzyme that breaks down cyclic nucleotides (cAMP/cGMP). While insulin *activates* phosphodiesterase to lower cAMP levels (antagonizing glucagon), the receptor itself is not a phosphodiesterase. * **Calcium-Calmodulin (C):** This is a second messenger system typically used by G-protein coupled receptors (GPCRs) linked to the $G_q$ protein (e.g., Oxytocin, $H_1$ receptors). Insulin does not primarily signal through this mechanism. * **Lipoprotein (D):** Lipoproteins (like LDL, HDL) are transport vehicles for lipids in the blood; they are not signaling receptors. **Clinical Pearls for NEET-PG:** * **GLUT4:** The only insulin-dependent glucose transporter, found primarily in skeletal muscle and adipose tissue. * **SH2 Domains:** Proteins involved in the insulin cascade (like PI3K) bind to phosphorylated tyrosine via their SH2 domains. * **Other RTKs:** Receptors for IGF-1, EGF, PDGF, and FGF also utilize the Tyrosine Kinase mechanism. * **Downregulation:** Chronic high insulin levels lead to receptor internalisation and downregulation, a key feature in Type 2 Diabetes/Insulin Resistance.

Question 79: What is the second messenger for oxytocin?

A. cAMP
B. cGMP
C. IP3-DAG (Correct Answer)
D. NO

Explanation: **Explanation:** The mechanism of action for hormones depends on their receptor type. Oxytocin acts via the **Gq protein-coupled receptor (GPCR)** pathway. When oxytocin binds to its receptor on the uterine or mammary smooth muscle, it activates **Phospholipase C (PLC)**. PLC cleaves membrane-bound Phosphatidylinositol 4,5-bisphosphate (PIP2) into two second messengers: **Inositol triphosphate (IP3)** and **Diacylglycerol (DAG)**. IP3 triggers the release of calcium from the sarcoplasmic reticulum, while DAG activates Protein Kinase C, leading to muscle contraction (labor and milk let-down). **Analysis of Options:** * **A. cAMP:** This is the second messenger for hormones acting via Gs/Gi pathways, such as Glucagon, ACTH, and ADH (V2 receptors). * **B. cGMP:** Utilized by Atrial Natriuretic Peptide (ANP) and Nitric Oxide (NO) via guanylyl cyclase activation. * **D. NO (Nitric Oxide):** This is a paracrine signaling molecule (gas) that acts as a primary messenger to stimulate cGMP production; it is not the second messenger for oxytocin. **High-Yield NEET-PG Pearls:** * **Gq Pathway Mnemonic:** Remember **"GOAT HAG"** for hormones using IP3-DAG: **G**nRH, **O**xytocin, **A**DH (V1 receptor), **T**RH, **H**istamine (H1), **A**ngiotensin II, and **G**astrin. * **Clinical Correlation:** Synthetic oxytocin (Pitocin) is used for induction of labor and management of postpartum hemorrhage (PPH) due to its potent contractile effect via the Gq pathway. * **ADH Contrast:** ADH uses **V1 receptors (Gq/IP3-DAG)** for vasoconstriction but **V2 receptors (Gs/cAMP)** for water reabsorption in the kidney.

Question 80: G-proteins function primarily as:

A. Hormone carriers
B. Hormone receptors
C. Second messengers
D. Signal transducers (Correct Answer)

Explanation: ### Explanation **Why "Signal Transducers" is Correct:** G-proteins (Guanine nucleotide-binding proteins) act as molecular switches that link extracellular signals (first messengers) to intracellular effectors. When a ligand binds to a **G-Protein Coupled Receptor (GPCR)**, the receptor undergoes a conformational change, activating the heterotrimeric G-protein ($\alpha, \beta, \gamma$ subunits). The G-protein exchanges GDP for GTP, dissociates, and "transduces" the signal to enzymes like Adenylate Cyclase or Phospholipase C. Thus, they serve as the essential bridge or **transducer** between the receptor and the cellular response. **Analysis of Incorrect Options:** * **A. Hormone carriers:** These are proteins like Albumin or Sex Hormone Binding Globulin (SHBG) that transport hydrophobic hormones through the bloodstream. * **B. Hormone receptors:** These are the initial docking sites (e.g., GPCRs, Tyrosine Kinase receptors) that recognize the ligand. G-proteins are peripheral membrane proteins associated with these receptors, not the receptors themselves. * **C. Second messengers:** These are small intracellular molecules (e.g., cAMP, $IP_3$, $DAG$, $Ca^{2+}$) produced *after* G-protein activation. G-proteins are the "messengers' delivery system," not the message itself. **High-Yield Clinical Pearls for NEET-PG:** * **G-protein Activity:** They possess intrinsic **GTPase activity** (primarily in the $\alpha$-subunit), which hydrolyzes GTP to GDP to terminate the signal. * **Cholera Toxin:** Inhibits GTPase activity of $G_s$, leading to constitutive activation of Adenylate Cyclase and permanent rise in cAMP (causing secretory diarrhea). * **Pertussis Toxin:** Inhibits $G_i$ (the inhibitory G-protein), also leading to increased cAMP levels. * **Nobel Prize Fact:** Robert Lefkowitz and Brian Kobilka won the 2012 Nobel Prize in Chemistry for their work on GPCRs.

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

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