Transmembrane JAK-STAT receptors MCQs With Answer

Transmembrane JAK-STAT receptors MCQs With Answer
Transmembrane JAK-STAT receptors mediate critical cytokine and growth factor signaling in cells, linking extracellular ligand binding to nuclear gene regulation via Janus kinases (JAKs) and Signal Transducers and Activators of Transcription (STATs). This concise, focused introduction for B. Pharm students covers receptor architecture, JAK-STAT activation, phosphorylation sites, negative regulators (SOCS, PIAS), cross-talk with other pathways, and pharmacological modulation by JAK inhibitors. Understanding these concepts is essential for grasping drug targets, therapeutic indications, adverse effects, and assay design in pharmacology and clinical research. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. Which domain of JAK proteins contains the catalytic tyrosine kinase activity?

• FERM domain
• SH2-like domain
• JH1 domain
• JH2 pseudokinase domain

Correct Answer: JH1 domain

Q2. Binding of cytokine to a transmembrane JAK-STAT receptor directly causes which immediate molecular event?

• Activation of receptor guanylate cyclase
• Dimerization or conformational change of the receptor leading to JAK activation
• Internalization of the receptor into lysosomes
• Covalent modification of STAT DNA-binding domain

Correct Answer: Dimerization or conformational change of the receptor leading to JAK activation

Q3. Which STAT protein is most commonly associated with interferon-gamma signaling?

• STAT1
• STAT3
• STAT5A
• STAT6

Correct Answer: STAT1

Q4. The FERM domain in JAK kinases primarily mediates:

• ATP binding to the kinase active site
• Interaction with the intracellular domain of cytokine receptors
• DNA binding of STATs
• Ubiquitination by E3 ligases

Correct Answer: Interaction with the intracellular domain of cytokine receptors

Q5. Which post-translational modification of STAT proteins is essential for dimerization and nuclear translocation?

• Palmitoylation
• Tyrosine phosphorylation
• Glycosylation
• Arginine methylation

Correct Answer: Tyrosine phosphorylation

Q6. SOCS proteins negatively regulate JAK-STAT signaling primarily by:

• Dephosphorylating STAT proteins directly
• Promoting ubiquitin-mediated degradation of signaling components and inhibiting JAK activity
• Blocking ligand binding at the extracellular receptor domain
• Sequestering DNA to prevent STAT binding

Correct Answer: Promoting ubiquitin-mediated degradation of signaling components and inhibiting JAK activity

Q7. Which JAK family member is most implicated in erythropoietin receptor signaling?

• JAK1
• JAK2
• JAK3
• TYK2

Correct Answer: JAK2

Q8. Gain-of-function mutations in JAK2 (e.g., V617F) are clinically associated with:

• Severe combined immunodeficiency
• Myeloproliferative neoplasms like polycythemia vera
• Type I diabetes mellitus
• Familial hypercholesterolemia

Correct Answer: Myeloproliferative neoplasms like polycythemia vera

Q9. PIAS proteins regulate STATs by which mechanism?

• Acting as phosphatases to remove phosphate groups
• SUMOylation and inhibition of STAT DNA-binding activity
• Cleaving STAT proteins proteolytically
• Enhancing STAT nuclear export by phosphorylation

Correct Answer: SUMOylation and inhibition of STAT DNA-binding activity

Q10. Which method is commonly used to detect STAT DNA-binding activity in molecular assays?

• ELISA for cytokine concentration
• Electrophoretic mobility shift assay (EMSA)
• Flow cytometry for surface markers
• Mass spectrometry of lipids

Correct Answer: Electrophoretic mobility shift assay (EMSA)

Q11. Tofacitinib is a small-molecule inhibitor primarily targeting which JAKs?

• Selective TYK2 only
• JAK1 and JAK3 preferentially, with some JAK2 inhibition
• EGFR kinase family
• STAT3 DNA-binding domain

Correct Answer: JAK1 and JAK3 preferentially, with some JAK2 inhibition

Q12. In JAK-STAT signaling, which residue class on receptors is phosphorylated to create STAT docking sites?

• Serine residues
• Threonine residues
• Tyrosine residues
• Lysine residues

Correct Answer: Tyrosine residues

Q13. Which cellular process provides a means to terminate JAK-STAT signaling rapidly by removing phosphates?

• Ubiquitination by E3 ligases
• Dephosphorylation by protein tyrosine phosphatases (PTPs)
• Methylation of DNA
• Lipidation of receptors

Correct Answer: Dephosphorylation by protein tyrosine phosphatases (PTPs)

Q14. STAT dimers bind to DNA sequences called:

• Enhancers only
• Interferon-stimulated response elements (ISRE) or GAS elements depending on STAT
• TATA boxes
• Poly-A tails

Correct Answer: Interferon-stimulated response elements (ISRE) or GAS elements depending on STAT

Q15. TYK2 is a JAK family member primarily involved in signaling by which cytokine family?

• Type I interferons and certain interleukins (e.g., IL-12, IL-23)
• Adrenergic hormones
• Transforming growth factor-beta (TGF-β)
• Insulin

Correct Answer: Type I interferons and certain interleukins (e.g., IL-12, IL-23)

Q16. Which structural feature distinguishes class I cytokine receptors that use JAK-STAT signaling?

• Seven transmembrane helices like GPCRs
• Single transmembrane helix with conserved Box1/Box2 motifs in the cytoplasmic tail
• Extracellular kinase domain
• Intrinsic guanylate cyclase activity

Correct Answer: Single transmembrane helix with conserved Box1/Box2 motifs in the cytoplasmic tail

Q17. Phosphorylation of STATs occurs on which specific amino acid for canonical activation?

• Serine in the transactivation domain only
• Tyrosine residue in the SH2-recruiting motif
• Lysine in the DNA-binding domain
• Cysteine residues forming disulfide bonds

Correct Answer: Tyrosine residue in the SH2-recruiting motif

Q18. A JAK inhibitor that binds the ATP pocket is termed a:

• Allosteric activator
• Type I ATP-competitive inhibitor
• Monoclonal antibody
• Peptidomimetic DNAzyme

Correct Answer: Type I ATP-competitive inhibitor

Q19. Which adverse effect is commonly monitored in patients receiving JAK inhibitors?

• Hyperthyroidism only
• Increased risk of infections and cytopenias
• Renal stone formation exclusively
• Peripheral neuropathy only

Correct Answer: Increased risk of infections and cytopenias

Q20. Dimerized phosphorylated STATs recognize DNA through which domain?

• SH3 domain
• DNA-binding domain containing a helix-loop-helix motif
• Homeobox domain
• Nuclear localization signal only

Correct Answer: DNA-binding domain containing a helix-loop-helix motif

Q21. Which experimental technique can quantify phosphorylation of STAT proteins in cell lysates?

• Northern blotting
• Western blot using phospho-specific antibodies
• Chromatin immunoprecipitation (ChIP) for RNA
• Blue native PAGE for lipids

Correct Answer: Western blot using phospho-specific antibodies

Q22. JAK3 deficiency in humans primarily leads to which immunological phenotype?

• Enhanced B-cell proliferation
• Severe combined immunodeficiency affecting T and NK cells
• Autoimmune hemolytic anemia
• Hyper IgE syndrome

Correct Answer: Severe combined immunodeficiency affecting T and NK cells

Q23. Cross-talk between JAK-STAT and MAPK pathways can occur via:

• Direct phosphorylation of receptor extracellular domain by MAPK
• Shared adaptor proteins and secondary phosphorylation events on STATs or receptors
• Exclusive localization in mitochondria
• Conversion of STAT to G-protein subunits

Correct Answer: Shared adaptor proteins and secondary phosphorylation events on STATs or receptors

Q24. Which laboratory model is commonly used to study receptor-mediated JAK-STAT activation in vitro?

• Pure lipid vesicle without proteins
• Cultured cells stimulated with recombinant cytokines and analyzed by immunoblot or reporter assays
• Whole-animal behavioral assays only
• In vitro glycosylation assays

Correct Answer: Cultured cells stimulated with recombinant cytokines and analyzed by immunoblot or reporter assays

Q25. Which therapeutic area has seen major application of JAK inhibitors?

• Autoimmune and inflammatory diseases such as rheumatoid arthritis and ulcerative colitis
• Acute bacterial infections primarily
• Topical antifungal therapy only
• Vitamin deficiency treatment

Correct Answer: Autoimmune and inflammatory diseases such as rheumatoid arthritis and ulcerative colitis

Q26. The pseudokinase (JH2) domain of JAKs primarily functions to:

• Serve as a catalytically active ATP-binding site
• Regulate the activity of the adjacent kinase (JH1) domain and mediate autoregulation
• Bind DNA directly
• Anchor JAK to the plasma membrane via lipidation

Correct Answer: Regulate the activity of the adjacent kinase (JH1) domain and mediate autoregulation

Q27. Which of the following is a common readout for STAT-dependent transcriptional activation in reporter assays?

• Luciferase activity driven by GAS or ISRE promoter elements
• Quantification of membrane cholesterol
• Measurement of mitochondrial ATP only
• Determination of extracellular calcium concentration

Correct Answer: Luciferase activity driven by GAS or ISRE promoter elements

Q28. Which cytokine signals primarily through the JAK-STAT pathway involving STAT6 activation?

• Interleukin-4 (IL-4)
• Interleukin-2 (IL-2)
• Interferon-gamma (IFN-γ)
• TNF-alpha

Correct Answer: Interleukin-4 (IL-4)

Q29. Resistance to JAK inhibitors in therapy may arise through which mechanism?

• Mutations in the ATP-binding pocket of JAKs or activation of parallel signaling pathways
• Complete absence of STAT proteins in patients
• Inability of drugs to cross the blood-brain barrier only
• Excessive dietary vitamin C intake

Correct Answer: Mutations in the ATP-binding pocket of JAKs or activation of parallel signaling pathways

Q30. Which statement best describes the role of transmembrane JAK-STAT receptors as drug targets?

• They are irrelevant because they do not affect gene expression
• They are attractive targets due to central roles in cytokine signaling, disease modulation, and availability of small-molecule inhibitors and biologics
• They can only be targeted by large proteins and are not druggable
• They exclusively regulate lipid metabolism and are not involved in immunity

Correct Answer: They are attractive targets due to central roles in cytokine signaling, disease modulation, and availability of small-molecule inhibitors and biologics

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