Intercellular and intracellular signaling pathways MCQs With Answer

Intercellular and intracellular signaling pathways are fundamental to understanding how drugs influence cells and tissues. This blog presents a focused set of MCQs tailored for M.Pharm students to deepen mechanistic knowledge and link signaling concepts to pharmacological intervention. Questions cover receptor classes (GPCRs, RTKs, JAK-STAT, Notch), second messengers (cAMP, IP3/DAG, cGMP), major cascades (MAPK, PI3K-Akt, Wnt), regulatory proteins (kinases, phosphatases, scaffolds, ubiquitin ligases, arrestins), apoptosis pathways, signal cross-talk and clinically relevant inhibitors. Use these items to test conceptual depth, refine reasoning about drug targets and pathway modulation, and prepare for advanced examinations in Cellular and Molecular Pharmacology. Answers are provided for self-assessment.

Q1. Which mode of intercellular signaling is specialized for long‑distance communication through the bloodstream?

• Autocrine signaling
• Paracrine signaling
• Endocrine signaling
• Synaptic signaling

Correct Answer: Endocrine signaling

Q2. Activation of phospholipase Cβ (PLCβ) generates which pair of second messengers from PIP2?

• cAMP and cGMP
• IP3 and DAG
• PIP3 and PI(3,4)P2
• Ca2+ and NO

Correct Answer: IP3 and DAG

Q3. In heterotrimeric G proteins, which subunit binds and hydrolyzes GTP to regulate downstream signaling?

• Alpha subunit
• Beta subunit
• Gamma subunit
• RGS protein

Correct Answer: Alpha subunit

Q4. Receptor tyrosine kinases (RTKs) transduce signals primarily by autophosphorylating which amino acid residues?

• Serine residues
• Tyrosine residues
• Histidine residues
• Lysine residues

Correct Answer: Tyrosine residues

Q5. Phosphoinositide 3‑kinase (PI3K) phosphorylates PIP2 to form which lipid second messenger that recruits PH‑domain containing proteins?

• PIP3
• IP3
• DAG
• cAMP

Correct Answer: PIP3

Q6. Nitric oxide produced by endothelial cells relaxes vascular smooth muscle primarily via activation of which intracellular pathway?

• IP3/DAG pathway
• cGMP/PKG pathway
• cAMP/PKA pathway
• MAPK/ERK pathway

Correct Answer: cGMP/PKG pathway

Q7. Which scaffold protein is well characterized for organizing the Ras→Raf→MEK→ERK kinase module?

• Arrestin
• KSR (kinase suppressor of Ras)
• PTEN
• SOCS

Correct Answer: KSR (kinase suppressor of Ras)

Q8. JAK‑STAT signaling initiates transcriptional responses by which mechanism?

• Receptor intrinsic tyrosine kinase activity phosphorylating STATs
• Cytoplasmic JAK tyrosine kinases associated with receptors phosphorylate STATs
• GPCR coupling to Gαs elevates cAMP to activate STATs
• SMAD proteins directly phosphorylate STATs

Correct Answer: Cytoplasmic JAK tyrosine kinases associated with receptors phosphorylate STATs

Q9. What is a canonical mechanism for homologous desensitization of G protein‑coupled receptors (GPCRs)?

• Ubiquitination by E3 ligases and proteasomal degradation
• Phosphorylation by GRKs followed by arrestin binding
• Direct proteolytic cleavage of the receptor extracellular domain
• Methylation of receptor cytoplasmic loops

Correct Answer: Phosphorylation by GRKs followed by arrestin binding

Q10. In the ubiquitin–proteasome system which enzyme class determines substrate specificity for ubiquitination?

• E1 ubiquitin‑activating enzymes
• E2 ubiquitin‑conjugating enzymes
• E3 ubiquitin ligases
• Deubiquitinating enzymes (DUBs)

Correct Answer: E3 ubiquitin ligases

Q11. Which enzyme family reverses tyrosine phosphorylation of RTK substrates to terminate signaling?

• Serine/threonine phosphatases (PP1/PP2A)
• Protein tyrosine phosphatases (PTPs)
• Lipid phosphatases like PTEN
• Ubiquitin ligases

Correct Answer: Protein tyrosine phosphatases (PTPs)

Q12. The drug sildenafil enhances NO signaling by inhibiting which phosphodiesterase isoform?

• PDE3
• PDE4
• PDE5
• PDE7

Correct Answer: PDE5

Q13. Constitutive activation of which signaling cascade (Ras→Raf→MEK→ERK) is a common driver of uncontrolled cell proliferation in cancer?

• PI3K-Akt pathway
• Wnt/β‑catenin pathway
• Ras-Raf-MEK-ERK (MAPK) pathway
• JAK-STAT pathway

Correct Answer: Ras-Raf-MEK-ERK (MAPK) pathway

Q14. In the canonical Wnt/β‑catenin pathway, what happens to β‑catenin in the absence of Wnt ligand?

• Stabilization by Frizzled receptor leading to nuclear translocation
• Phosphorylation by GSK3 within destruction complex followed by ubiquitination and proteasomal degradation
• Direct dephosphorylation by PP2A leading to gene activation
• Sequestration by cadherins at the plasma membrane preventing degradation

Correct Answer: Phosphorylation by GSK3 within destruction complex followed by ubiquitination and proteasomal degradation

Q15. Notch receptor activation triggers downstream transcription primarily through which event?

• G-protein activation and second messenger generation
• Proteolytic cleavage releasing the Notch intracellular domain that translocates to the nucleus
• Receptor dimerization and autophosphorylation on tyrosines
• Activation of adenylate cyclase and increased cAMP

Correct Answer: Proteolytic cleavage releasing the Notch intracellular domain that translocates to the nucleus

Q16. Which second messenger binds to IP3 receptors to directly mobilize Ca2+ from the endoplasmic reticulum?

• DAG
• IP3
• cAMP
• cGMP

Correct Answer: IP3

Q17. The intrinsic (mitochondrial) apoptotic pathway leads to apoptosome assembly and activation of which initiator caspase?

• Caspase-3
• Caspase-8
• Caspase-9
• Caspase-1

Correct Answer: Caspase-9

Q18. Beyond blocking G‑protein coupling, arrestin proteins also contribute to GPCR regulation by doing which of the following?

• They phosphorylate receptors to initiate signaling
• They mediate receptor internalization and block further G-protein coupling while also acting as scaffolds for alternative signaling
• They act as E3 ubiquitin ligases to degrade receptors
• They serve as GEFs to activate G proteins

Correct Answer: They mediate receptor internalization and block further G-protein coupling while also acting as scaffolds for alternative signaling

Q19. GPCR-induced transactivation of epidermal growth factor receptor (EGFR) commonly involves which mechanism?

• Direct phosphorylation of EGFR by Gα subunits
• Metalloprotease-mediated cleavage of membrane-bound ligands (e.g., HB‑EGF) releasing RTK ligands
• GPCRs dimerize with EGFR and form heterodimers
• cAMP-dependent activation of EGFR kinase domain

Correct Answer: Metalloprotease-mediated cleavage of membrane-bound ligands (e.g., HB‑EGF) releasing RTK ligands

Q20. In the canonical NF‑κB activation pathway, which kinase complex phosphorylates IκB to trigger its ubiquitination and degradation?

• mTORC1
• IκB kinase (IKK) complex
• PKA
• MAPK kinase (MEK)

Correct Answer: IκB kinase (IKK) complex

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