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BL A512 -- Signal Transduction Fall -- 1998 -- Prof. Stark
Final Exam -- Tuesday May 5, 1998 -- 8-9:50 am-- 100 points

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1. Describe the technique of SSCP (Single Stranded Conformational Polymorphism) to test whether mutations in a candidate gene mediate a disorder such as retinitis pigmentosa. (2 points)

2. In the human olfactory sense, (a) what type of receptor molecule is used? (b) How many different receptor molecules are there? and (c) What is the next (downstream) molecule with its olfactory-specific component? (3 points)

3. To (a) what state of (b) what molecule does arrestin bind? (c) Why was arrestin also called S-antigen? (3 points)

4. (a) Why might the compartmentalization of the phototransduction machinery of Drosophila be referred to as a "transduceosome?" (b) Does the same compartmentalization apply in vertebrate visual transduction? (c) Why or why not? (3 points)

5. What are the specialized domains of Drk (downstream of receptor tyrosine kinase) to mediate the cascade from sevenless to son of sevenless? (1 point)

6. Why is the ras molecule is localized where it is? (1 point)

7. Describe the nature of a GPI anchor such as is used to attach the CNTF-R-alpha (ciliary neurotrophic factor receptor) to the membrane. (1 point)

8. (a) How does angiogenesis lead to diabetic retinopathy and (b) what is the preventative treatment? (c) Why is regulation of angiogenesis relevant to cancer? (3 points)

9. (a-b) What 2 aspects of the STAT molecule allow it to dimerize for transcriptional activation? (c) What other molecule makes STAT to have one of those 2 aspects? (d) What does STAT stand for? (4 points)

10. What receptor and what ligand probably signal the appropriate T-cell apoptosis and the premature T-cell death in AIDS? (2 points)

11. Describe the number and locations of tumors in hereditary and nonhereditary retinoblastoma. (2 points)

12. What famous ligand involved, say, in cancer, signals through the frizzled receptor? What is the Drosophila homologue? How do Frzb's, those Frizzled-like molecules with a ligand-binding domain but lacking the transmembrane domain, interfere with signalling? (3 points)

13. RXR dimerizes with (a) what type or types of molecule(s) to bind two response elements which are separated by (b) what range of distances from eachother? (c) What is the type of metal-binding domain responsible for this binding to the response element? (3 points)

14. What is a DNA ladder and to what does it apply? (2 points)

15. Describe the approximate size and configuration of one molecule of growth factor (like PDGF or CNTF). What role does the ligand binding play in the organization/activation of the receptor? (2 points)

16. What kind of a virus is Roux sarcoma virus? What gene is inactivated in this virus which has homologues in several other signalling cascades? (2 points)

17. Describe the color vision capabilities of vertebrates, mammals, new and old world monkeys, and humans. Relate this to color blindness in men and women and to X-inactivation in monkeys and to the divergent evolution of G-protein coupled receptors. (4 points)

18. Describe or draw the cyclic nucleotide gated channel with respect to membrane localization and ligand binding site. (2 points)

19. Compare the role of calcium in adaptation/transduction in vertebrate/ invertebrate phototransduction addressing (hint) GC (guanylate cyclase) and the SOC (storage operated calcium channel). (3 points)

20. What does HH (hedgehog) have to do with development of the adult Drosophila compound eye from the imaginal disk? HH signals to alter what growth factor homologue? (2 points)

21. What plant signalling molecule is related to the herbicides 2,4-D, 2,3,4-T and deadly agent orange (1 point)

22. SOS (son of sevenless) is a GNRP (guanine nucleotide releasing protein). What molecule does SOS act on and specifically, what does it do to that molecule (2 points)

23. What is gusducin? (1 point)

24. A lot of diverse strains mice are blind because of alterations in the 22 exon cGMP PDE (phosphodiesterase) beta-subunit gene. What is so unusual about the alterations in this gene? What would be the condition of the cyclic nucleotide gated channel in the rods of these mice before the rods degenerate? (2 points)

25. A while ago, Patched (Ptc) was a candidate for the HH (hedgehog) receptor. Now, the receptor is thought to be what molecule? In a news item entitled "pass the butter," what was proposed to regulate long- vs. short-range HH signalling? (2 points)

26. A pulse of light interrupting a long dark period in a light dark cycle disrupts the appropriate regulation of long- and short-day flowering plants. What hormone is involved? Describe the relative disruption or lack of disruption for red followed by far red light and also for far red followed by red light. Why does it come out this way? (4 points)

27. What is the current thinking on how ras activates raf? (1 point)

28. In the nuclear hormone superfamily, retinol (vitamin A) is converted to retinal which is then converted to what signalling hormone? What proteins bind this hormone in the cytoplasm vs in the nucleus? (3 points)

29. What is ICE? What type of molecule is it (something more specific than "protein")? Which C. elegans molecule in this signalling pathway is most like ICE? (3 points)

30 In familial adenomatous polyposis coli (APC), an important tumor suppressor is involved. Name one other important molecule in this signalling pathway. (1 point)

31. At what step in a signalling pathway (where in the cascade) is Notch? Describe the Notch molecule and its localization. (3 points)

32. Describe the different roles of rods vs. cones in acuity vs. sensitivity. (2 points)

33. The Arabidosis DET2 gene codes for a 262 amino acid protein with homology to mammalian 5-alpha-reductase. This pertains to what kind of signalling in plants? (1 point)

34. Functionally, what kind of molecule is FMRF-amide? (An answer like "second messenger" or "transcription factor" is sought.). What molecule covered earlier in the semester is is like the molecule downstream to FMRF-amide in its signalling pathway? (2 points)

35. Contrast the potassium (K+) uptake channel from Arabidosis thaliana (KAT) and TRP (transient receptor potential) with Shaker in terms of minor differences given the overall similarity. (2 points)

36. What is the difference between vasculogenesis and angiogenesis. Name (an abbreviation will suffice) a ligand involved in one of these processes. (2 points)

37. Mutants of the daf-2 gene in C. elegans interfere with what stage in the life cycle? What is the homologous vertebrate signal molecule? (2 points)

38. Bax interacts with and counteracts the actions of (a) what protein in (b) what process? (2 points)

39. Responsivities to all-trans vs. 9-cis retinoic acids define what two families of receptors? (2 points)

40. In the rod outer segment, how many G-protein molecules are there relative to rhodopsin molecules? How does this relate to amplification? (2 points)

41. What is the function of bacteriorhodopsin? (1 point)

42. Mutants of the Drosophilavisual transduction gene norpA have what alteration in their phenotype? What important signalling molecule does norpA code for? What molecule is at the same step (downstream of transducin) for vertebrate phototransduction? (3 points)

43. "Downstream of raf 1 (Dsor) is a MAPK-kinase." Analyse this statement in terms of what Dsor does to what molecule. Where is this taking place cellularly and where is this in the cascade relative to boss (bride of sevenless)? (4 points)

44. What is an "orphan" receptor? (1 point)

45. Ashburner's classic observation of "puffs" on Drosophila polytene chromosomes pertains to what class of ligands used in signalling? (1 point)

46. Name a tissue involved in developmental induction which expresses sonic hedgehog. (1 point)

47. What is the TUNEL technique used for? (1 point)

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