cell signalling part 3

1. Which of the following statements about Wnt/β-catenin signalling is correct?

2. In apoptosis, the release of cytochrome c from mitochondria leads to activation of:

3. Which of the following is TRUE about phosphatidylinositol 4,5-bisphosphate (PIP2) in GPCR signalling?

4. In the cAMP signalling pathway, which of the following enzymes directly converts ATP into cAMP?

5. Which of the following statements about receptor tyrosine kinases (RTKs) is correct?

6. Which of the following pathways is primarily involved in the regulation of cell cycle progression?

7. Which of the following is a second messenger involved in the activation of protein kinase C (PKC)?

8. Which of the following is a function of the Notch signaling pathway?

9. Which of the following is a characteristic feature of G-protein coupled receptors (GPCRs)?

10. Which of the following signaling molecules binds to nuclear receptors?

11. Which of the following organelles is involved in apoptosis?

12. Cancer cells secrete channels such as VEGF for angiogenesis, whose target cells are:

13. Which of the following is most likely to be activated in non-canonical Wnt pathway?

14. Which one of the following is a type of intercellular junction in animal cells?

15. The essential mineral required for cell adhesion molecule, cadherin is:

16. Receptors for signaling for steroid hormones are located at:

17. Which of the following proteins/enzyme leads to apoptosis?

18. cAMP is directly involved in regulation of:

19. Which of the following is NOT a second messenger?

20. Which of the following signaling molecules enters the cell to initiate its action?

21.

• Insulin stimulates PI3K-Akt → glucose uptake

• PI3K inhibitor applied → Akt blocked, MAPK unaffected

• Ras-MAPK inhibitor applied → proliferation blocked, glucose uptake unaffected

Question:

• Explain pathway specificity

• How can this data inform targeted therapy?

22.

• Cells treated with γ-secretase inhibitor → NICD not released

• Target gene transcription blocked

• Overexpression of NICD restores transcription

Question:

• Mechanism of Notch inhibition?

• Predict outcome if ligand overexpressed

23.

APC mutation in colon carcinoma:

• β-catenin accumulates in cytoplasm/nucleus

• TCF/LEF targets constitutively active

• Addition of Wnt ligand → no further effect

Question:

• Explain why Wnt ligand has no effect

• Predict what happens if β-catenin is knocked down

24.

• JAK mutant unable to phosphorylate STAT

• Constitutively active Ras introduced → partial STAT phosphorylation restored

Question:

• Explain how Ras compensates JAK defect

• Implications for signalling redundancy

25.

A GPCR activates both Gs and Gq. Inhibitors used:

• Adenylate cyclase inhibitor → cAMP blocked

• PLC inhibitor → DAG/IP₃ blocked → PKC inactive

• Ca²⁺ flux abolished

Question:

• How does dual G-protein activation regulate cellular response?

• Predict MAPK activity if only PLC inhibited

26.

Mutant analysis:

• Patched KO → Smoothened constitutively active → Gli activator accumulates

• Smoothened KO → Hedgehog ligand cannot activate Gli

Question:

• Explain hierarchy of Patched-Smoothened-Gli

• Predict outcome of double knockout

27.

TGF-β stimulation in tumour cells:

• SMAD2/3 phosphorylated, translocates to nucleus

• Target gene transcription blocked

• ERK phosphorylation strongly induced

• Inhibition of MAPK restores SMAD transcription

Question:

• Mechanism of transcriptional blockade?

• How does MAPK-SMAD cross-talk influence tumour progression?

28.

Proteasome inhibitor treatment:

• IκB degradation is blocked → NF-κB inactive

• β-catenin accumulates → Wnt target genes active

• Addition of TNF-α does not induce NF-κB

• Wnt ligand addition has no effect

Question:

• Explain the role of proteasome in these pathways.

• Predict how mutation in β-TrCP would change the outcome.

29.

Cells with Ras G12V mutation are treated with a PI3K inhibitor. Observations:

• ERK phosphorylation remains high

• Akt phosphorylation is blocked

• Cell proliferation continues partially

Question:

• Explain how Ras mutation affects MAPK pathway despite PI3K inhibition.

• How does this inform targeted therapy strategies?

30.

A novel RTK “X” is overexpressed in a cell line. Experiments show:

1. Ligand binding occurs normally

2. Autophosphorylation is completely blocked

3. MAPK cascade is inactive

4. PI3K-Akt pathway partially active

5. Addition of a GPCR agonist partially restores MAPK activity

Question:

• Explain the mechanism of MAPK restoration by GPCR agonist.

• Predict the outcome if both RTK X and GPCR are inhibited simultaneously.

31. Constitutive active MAPK → effect of Raf inhibitor?

32. PTEN loss → cellular effect?

33. SH2 domain mutation in adaptor → effect?

34. RTK mutation prevents Grb2 binding → effect on Ras-MAPK?

35. Akt phosphorylation rescued by Ras activation in JAK mutant cells → suggests?

36. PLCγ knockout → which pathway disrupted?

37. RTK overexpression (HER2) without ligand → effect?

38. PI3K inhibitor applied → Akt phosphorylation blocked, MAPK unaffected. Why?

39. Ras G12V mutation → effect?

40. EGFR lacking kinase domain binds EGF. Observation?

41. A Ca²⁺-dependent kinase inhibitor blocks DAG-independent PKC activation. Likely effect?

A. MAPK signalling impaired in GPCR pathway
B. cAMP unaffected
C. Ras-MAPK normal
D. PI3K enhanced

42. Cross-talk: GPCR (Gs) enhances RTK-mediated PI3K activation. Mechanism?

43. Gq activation increases intracellular Ca²⁺. Which protein senses it?

44. β-arrestin knockout cells:

45. DAG is analogue of:

46. Pertussis toxin blocks Gi. What happens to AC and cAMP?

47. Forskolin used in cAMP signalling cells. Observation?

48. Cross-talk: GPCR activates Src → transactivation of EGFR. Result?

49. A Gs protein mutation locks it in GTP-bound state. Effect?

50. A GPCR activates Gαq leading to PLC activation. Cells treated with PLC inhibitor show:

A. No IP₃/DAG production → Ca²⁺ and PKC inactive
B. cAMP production stops
C. MAPK activation is unaffected
D. PI3K-Akt signalling enhanced