Intracellular signaling pathways and extracellular signals MCQs With Answer

Introduction: Intracellular signaling pathways and extracellular signals are central to pharmacology and drug action. This topic covers signal transduction mechanisms including receptors (GPCRs, RTKs, ion channels), second messengers (cAMP, IP3, DAG, Ca2+), kinases and phosphatases, G-proteins, MAPK, PI3K-Akt, JAK-STAT, and nuclear receptors. Understanding receptor activation, signal amplification, desensitization, cross-talk, and pharmacological modulation (agonists, antagonists, inhibitors) is essential for B. Pharm students to link molecular events to therapeutic strategies and adverse effects. Emphasis is placed on clinical targets, mechanism-based drug design, and experimental assays used in research. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. Which intracellular second messenger is directly produced by adenylate cyclase activity?

• Inositol 1,4,5-trisphosphate (IP3)
• Cyclic AMP (cAMP)
• Diacylglycerol (DAG)
• Calcium ion (Ca2+)

Correct Answer: Cyclic AMP (cAMP)

Q2. Activation of Gq-coupled GPCRs primarily leads to which immediate signaling event?

• Increase in cAMP via adenylate cyclase
• Activation of phospholipase C and generation of IP3 and DAG
• Tyrosine phosphorylation of intracellular substrates
• Direct opening of potassium channels

Correct Answer: Activation of phospholipase C and generation of IP3 and DAG

Q3. Which kinase is classically activated by increased intracellular cAMP?

• Protein kinase C (PKC)
• Mitogen-activated protein kinase (MAPK)
• Protein kinase A (PKA)
• Phosphoinositide 3-kinase (PI3K)

Correct Answer: Protein kinase A (PKA)

Q4. Receptor tyrosine kinases (RTKs) are typically activated by which mechanism?

• Ligand-induced dimerization and autophosphorylation
• Guanine nucleotide exchange on G-proteins
• Direct binding of cyclic nucleotides
• Proteolytic cleavage in the extracellular domain

Correct Answer: Ligand-induced dimerization and autophosphorylation

Q5. Which pathway is most directly involved in promoting cell survival and growth and is a major drug target in cancer?

• cGMP-PKG pathway
• PI3K-Akt-mTOR pathway
• IP3/Ca2+ signaling
• JAK-STAT pathway

Correct Answer: PI3K-Akt-mTOR pathway

Q6. What is the primary function of protein phosphatases in signaling?

• To phosphorylate serine, threonine, or tyrosine residues
• To dephosphorylate proteins and terminate kinase signals
• To synthesize second messengers
• To degrade receptors via proteasome

Correct Answer: To dephosphorylate proteins and terminate kinase signals

Q7. Which second messenger directly causes release of Ca2+ from the endoplasmic reticulum?

• cAMP
• DAG
• IP3
• cGMP

Correct Answer: IP3

Q8. Beta-adrenergic receptors that stimulate adenylate cyclase are coupled to which G-protein subtype?

• Gi
• Gs
• Gq
• G12/13

Correct Answer: Gs

Q9. Which of the following describes receptor desensitization mediated by GRKs and arrestins?

• Enhanced receptor ligand affinity
• Phosphorylation of receptor, arrestin binding, and internalization
• Receptor conversion into a constitutively active form
• Activation of downstream transcription without ligand

Correct Answer: Phosphorylation of receptor, arrestin binding, and internalization

Q10. In the JAK-STAT signaling cascade, what is the immediate consequence of cytokine binding to its receptor?

• Activation of receptor-associated Janus kinases and STAT phosphorylation
• Activation of adenylate cyclase and increased cAMP
• Cleavage of receptor and nuclear translocation of intracellular domain
• Direct production of IP3 and DAG

Correct Answer: Activation of receptor-associated Janus kinases and STAT phosphorylation

Q11. Which molecule is a common lipid second messenger that recruits proteins with PH domains to membranes?

• Phosphatidylinositol 4,5-bisphosphate (PIP2)
• Phosphatidylinositol 3,4,5-trisphosphate (PIP3)
• Diacylglycerol (DAG)
• Sphingosine-1-phosphate (S1P)

Correct Answer: Phosphatidylinositol 3,4,5-trisphosphate (PIP3)

Q12. Which pharmacological agent directly inhibits receptor tyrosine kinases by competing with ATP at the catalytic site?

• Monoclonal antibody against receptor extracellular domain
• Small-molecule tyrosine kinase inhibitor (e.g., imatinib)
• Phosphodiesterase inhibitor
• Allosteric GPCR agonist

Correct Answer: Small-molecule tyrosine kinase inhibitor (e.g., imatinib)

Q13. Which process exemplifies signal amplification in a typical GPCR-adenylate cyclase pathway?

• One receptor activates many G-proteins, each activating many adenylate cyclase molecules
• Direct transcription factor binding by receptor without intermediates
• One ligand binds many receptors simultaneously
• Rapid degradation of second messengers

Correct Answer: One receptor activates many G-proteins, each activating many adenylate cyclase molecules

Q14. Nitric oxide (NO) exerts vasodilatory effects primarily through which intracellular target?

• Adenylate cyclase to increase cAMP
• Guanylate cyclase to increase cGMP
• Phospholipase C to generate IP3
• MAPK to induce gene expression

Correct Answer: Guanylate cyclase to increase cGMP

Q15. Which of the following best characterizes a partial agonist at a receptor?

• Produces the same maximal response as a full agonist at saturating concentrations
• Blocks receptor activation by full agonists but has no intrinsic activity
• Produces a submaximal response even at full receptor occupancy
• Has higher affinity than the endogenous ligand but no efficacy

Correct Answer: Produces a submaximal response even at full receptor occupancy

Q16. Cross-talk between signaling pathways refers to which phenomenon?

• Complete independence of parallel signaling cascades
• Interaction where one pathway modulates components of another
• Degradation of all second messengers simultaneously
• Formation of receptor heterodimers only

Correct Answer: Interaction where one pathway modulates components of another

Q17. The MAPK/ERK cascade is typically activated downstream of which receptor type?

• Ionotropic neurotransmitter receptors only
• Receptor tyrosine kinases and some GPCRs via Ras activation
• Nuclear hormone receptors
• Guanylate cyclase-linked receptors exclusively

Correct Answer: Receptor tyrosine kinases and some GPCRs via Ras activation

Q18. Which mechanism is often used by cells to terminate cAMP signaling?

• Activation of phospholipase C to consume cAMP
• Hydrolysis of cAMP by phosphodiesterases (PDEs)
• Export of cAMP via ABC transporters
• Conversion of cAMP into IP3

Correct Answer: Hydrolysis of cAMP by phosphodiesterases (PDEs)

Q19. In apoptosis, the intrinsic (mitochondrial) pathway is initiated by which event?

• Activation of death receptors on the cell surface
• Mitochondrial outer membrane permeabilization and cytochrome c release
• Cleavage of extracellular matrix proteins
• Inhibition of caspases by IAPs

Correct Answer: Mitochondrial outer membrane permeabilization and cytochrome c release

Q20. Biased agonism at GPCRs refers to what concept?

• Agonists that bind irreversibly to receptors
• Ligands that preferentially activate certain downstream pathways over others
• Agonists that cannot be desensitized
• Non-specific activation of all receptor subtypes

Correct Answer: Ligands that preferentially activate certain downstream pathways over others

Q21. Which experimental assay is commonly used to measure activation of a transcription factor downstream of signaling?

• Patch-clamp electrophysiology
• Luciferase reporter gene assay
• Flow cytometry for cell size
• Mass spectrometry of lipids

Correct Answer: Luciferase reporter gene assay

Q22. Which protein family mediates ubiquitin-dependent degradation of signaling proteins and contributes to signal termination?

• Kinases
• E3 ubiquitin ligases
• GTPases
• Phosphatases

Correct Answer: E3 ubiquitin ligases

Q23. Which statement best explains receptor internalization leading to downregulation?

• Internalized receptors are always recycled back to the membrane unchanged
• Internalization can lead to lysosomal degradation and reduced receptor number
• Internalization increases receptor surface expression
• Internalization prevents ligand binding but increases signaling

Correct Answer: Internalization can lead to lysosomal degradation and reduced receptor number

Q24. Which enzyme converts phosphatidylinositol 4,5-bisphosphate (PIP2) into DAG and IP3?

• Phospholipase A2 (PLA2)
• Phospholipase C (PLC)
• Phosphatidylinositol 3-kinase (PI3K)
• Phospholipase D (PLD)

Correct Answer: Phospholipase C (PLC)

Q25. Which class of drugs increases intracellular cGMP by inhibiting phosphodiesterase-5 (PDE5)?

• Beta-blockers
• Nitrates
• Phosphodiesterase-5 inhibitors (e.g., sildenafil)
• Calcium channel blockers

Correct Answer: Phosphodiesterase-5 inhibitors (e.g., sildenafil)

Q26. STAT proteins, once phosphorylated, exert their effects by which mechanism?

• Acting as membrane ion channels
• Translocating to the nucleus and regulating gene transcription
• Generating second messengers like DAG
• Activating G-proteins at the membrane

Correct Answer: Translocating to the nucleus and regulating gene transcription

Q27. Which signaling adapter protein binds phosphotyrosine residues via its SH2 domain?

• GAP (GTPase-activating protein)
• SOS (guanine nucleotide exchange factor)
• Grb2
• Calmodulin

Correct Answer: Grb2

Q28. The intrinsic activity of an agonist refers to which property?

• Its affinity for the receptor only
• The maximal response it can elicit when occupying receptors
• Its ability to be metabolized by the liver
• Its selectivity for receptor subtypes only

Correct Answer: The maximal response it can elicit when occupying receptors

Q29. Which mechanism explains how calcium-calmodulin activates downstream kinases?

• Calcium binds to calmodulin causing a conformational change that activates kinases like CaMK
• Calmodulin phosphorylates kinases directly
• Calcium removes phosphate groups from kinases
• Calcium-calmodulin degrades kinases via proteasome

Correct Answer: Calcium binds to calmodulin causing a conformational change that activates kinases like CaMK

Q30. Which therapeutic strategy targets downstream signaling rather than the receptor itself to overcome resistance in cancer?

• Monoclonal antibodies against the receptor extracellular domain
• Small-molecule inhibitors of signaling kinases (e.g., MEK, Akt inhibitors)
• Ligand supplementation to outcompete antagonists
• Vaccination against the receptor

Correct Answer: Small-molecule inhibitors of signaling kinases (e.g., MEK, Akt inhibitors)

G S Sachin

I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.

Mail- Sachin@pharmacyfreak.com