BL A512 -- Signal Transduction, Spring, 2002, Prof. Stark
Final exam -- Tuesday May 7, 2002, 100 points

1. Explain how RIP (regulated intracellular proteolysis) creates an analogy between the Notch pathway and Alzheimer's pathway. (2 points)

Recent evidence has S3 cleavage at membrane releasing intracellular transcriptionally active domain. Amyloid precursor protein is cleaved to make beta amyloid that clumps into plaques.

2. One of the "little-known-well-known" facts you have been exposed (subjected) to is that the glucocorticoid receptor is in the cytoplasm until glucocorticoids bind it. By contrast where do the other 50 members of this superfamily (in humans) start out? (1 point)

Steroid hormone receptors are nuclear.

3. Molecules like the vitamin D receptor and the thyroid hormone receptor are thought to function by forming heterodimers with what molecule? (1 point)

RXR

4. Where is Fas ligand, and what happens if it activates its receptor? (2 points)

It is an extracellular ligand that binds Fas at the membrane and stimulates the apoptotic pathway.

5. What activates gene transcription when Wnt binds to its receptor, and why doesn't it do that when the pathway is not activated? (2 points)

With, beta catenin goes into the nucleus to activate transcription, without it is phosphorylated and tagged for destruction by proteosome.

6. How does p53 function and what happens with regard to p53 and its regulation of apoptosis in cancer? (2 points)

it is proapoptotic and that function is lost in cancer

7. Ethylene insensitive mutants are thought to affect a receptor that has what enzymatic activity? (1 point)

histidine kinase

8. Why did G. Martin use "pass the butter" for her perspective about hedgehog? (1 point)

cholesterol is attached

9. Receptor tyrosine kinases [RTKs] are, of course, very famous. Oddly, those same words [letters] are rearranged to "Trk." For what type of signalling that occurs where? (2 points)

for NGF, a ligand from target, where Trk is at nerve terminal touching target

10. What type of molecule is the EGF receptor? (1 point)

RTK

11. How can it be that a gene as fundamental as rhodopsin's can be mutated in many cases of retinitis pigmentosa (where people can still see, with their rods, for 1-2 decades)? (2 points)

autosomal dominant implies there is a functioning allele and the mutant allele has gain of function (toxic produce, in lay terms)

12. What activates gene transcription when Hh binds to its receptor, and why doesn't it do that when the pathway is not activated? (2 points)

GLI/CI 155 is active, cleaved 75 is repressor

13. What happens in C. elegans if the ced-3 and ced-4 genes are mutated? (1 point)

131 cells that should have died do not

14. If farnesyl transferase acted on a molecule in a signal transduction cascade, how would that molecule's location be altered? (1 point)

attached to membrane like ras and G (gamma) also an enhanced response to abscissic acid gene in Arabidopsis is a farnesyl transferase

15. What does eNOS (endothelial nitric acid synthase) activity do to skeletal muscle? How does prior exercise (training) affect this? (1 point)

enhance blood flow and training helps this

16. Since 2000, bitter and sweet receptors have been found. What type of molecules were they and what expedited the isolation? (2 points)

G protein coupled receptors. Helped to have mutations localized and look there in the genome

17. "Deadly agent orange" functioned by mimicing what molecule? (1 point)

auxin

18. What does a DNA ladder tell you? (1 point)

DNA chopped into 1x, 2x, 3x, etc a certain length as happens in apoptosis

19. In a paper you were not assigned, molecules called Frzb's were discussed having the same cysteine rich domain as the extracellular portion of Frizzled. Use what you know about signalling pathways to state what pathway they would interfere with and to speculate as to how they would interfere. (2 points)

They would sponge up the Wnt so it could not stimulate the Frizzled

20. RXR and RAR are distinguished pharmacologically by what? (2 points)

for RXR, 9-cis>all trans RA, for RAR - 9-cis and all trans are equally effective

21. How does ras compare with the heterotrimeric G protein in size and function of GAP and GNRP? (3 points)

smaller than even the alpha, ras-GTP needs GAP but alpha has that activity itself. ras-GDP needs SOS, while G-protein-coupled receptor does that for alpha

22. What does 5 alpha reductase have to do with steroids in plants and animals? (2 points)

involved in brassinosteroid synthesis, testosterone -> dihydrotestosterone

23. The oncogene Abl, relates to tyrosine kinase function of its proto-oncogene. When defective, what kind of cancer results? (1 point)

leukemia

24. Describe the Notch molecule. (2 points)

big, one membrane pass, 36 EGR repeats and 3 lin-notch repeats outside, 6 ankyrin repeats and 1 PEST inside

25. What type of molecule is a receptor for a prostaglandin? (1 point)

G protein coupled receptor

26. Sometimes the genetic jargons "gain of function" and "loss of function" are applied to genes involved in cancer. What are the corresponding cancer jargons? (2 points)

oncogene, tumor suppressor

27. After some confusion about two putative receptors for hedgehog, which was shown to be the receptor and how does it interact with the other? (2 points)

patched represses smoothened unless HH binds patched

28. What is Drosophila dpp (decapentaplegic) related to (and thus where would you find it)? (2 points)

TGF-beta, BMP, it's an extracellular ligand

29. What is phytochrome a receptor for? (1 point)

red, far-red light

30. How does the candidate gene approach work in finding causes of blindness? (2 points)

pick likely genes and compare exon sequences for normal vs. affected using SSCP

31. What do you call the process that is altered in diabetic retinopathy (and cancer) when new blood vessels form? (1 point)

angiogenesis

32. One type of NOS is inducible. Inducible by what and located in what cell type? (2 points)

cytokines, macrophages

33. Suppose your metabolism had to start with beta-carotene. Recall from earlier this semester that beta-carotene is a dimer of vitamin A. How would your metabolism produce retinoic acid from this precursor? (2 points)

retinol -> retinal -> retinoic acid

34. What advantage would confocal microscopy have in comparison with standard fluorescence microscopy? (1 point)

optical sectioning (low depth of focus)

35. How come there's only one R7 cell when sevenless is expressed in many cells in each developing ommatidium? (1 point)

only one sev expressing cell contacts the R8 that expresses boss at the right time

36. What is the general meaning of the term "orphan receptor?" (1 point)

don't know the ligand yet

37. What is mutated in basal cell nevus syndrome (carcinoma)? (1 point)

patched

38. How do COX-1 and COX-2 differ in terms of regulation of expression? (2 points)

1 constituitively expressed all over the place (including stomach), 2 upregulated

39. On B cells, what is that Y-shaped molecule that serves as an antigen receptor? (1 point)

antibody

40. How is it that visual transduction proteins in Drosophila happen to be near eachother (allowing efficiency and quick response, presumably)? (2 points)

INAD is PDZ domain protein holding transduceocome

41. What is the enzyme that releases arichidonic acid? (1 point)

PLA2

42. What does p53 have to do with cell division? (1 point)

p53 via p21 halts cell cycle

43. Plants specialize in what instead of receptor tyrosine kinases that animals use? (1 point)

serine-threonine

44. Explain what a sequence like AGGTCA-(1 to 5 nucleotide space)-AGGTCA would suggest to you. (2 points)

the RARE for RAR

45. The receptor tyrosine kinase pathway differs considerably from pathways like Notch, Hedgehog and Wingless with respect to the nuclear factors, according to Brivanlou and Darnell, 2002. How? (2 points)

for RTK, factors stay in nucleus, for others, there is cytoplasm-nucleus traffic

46. Why did I put Robert Frost's "Fire and Ice" ("Some say the world will end in fire, Some say in ice") in your lecture outline? (1 point)

ICE interleukin-1 beta-converting enzyme

47. What signal molecule is associated with cadherin? (1 point)

beta-catenin

48. What would Hedgehog do in the eye imaginal disk? (1 point)

secreted from posterior toward anterior to move morphogenetic furrow

49. Name the Notch ligands. (2 points)

Delta and Serrate

50. What does MSG (monosodium glutamate) do and via what type of receptor? (2 points)

stimulates umami taste in a way like glutamate affects the nervous system channel

51. Where do you find the famous molecules CD4 and CD8, and what do they do there? (2 points)

on helper and killer T cells

52. What "type" (with reference to receptor type) of signalling uses SMADs and what are SMADs (2 points)

involved in carrying into the nucleus transcriuptional regulation in TGF-beta signalling

53. In Drosophila phototransduction, what is immediately downstream of rhodopsin, and what specific molecule, coded by the norpA (no receptor potential) gene is the next step? (2 points)

G protein, PLC-beta

54. How many olfactory receptor molecules do people have? (1 point)

lots (500-1000)

55. What seems so unusual about steroid receptors in plants (by contrast with those of animals)? (1 point)

they bind steroid extracellularly

56. How do prostaglandins get out of cells? (1 point)

transporter

57. What does cAMP do inside olfactory receptor cells to mediate excitation? (1 point)

gate a cyclic nucleotide gated calcium channel

58. MAPKs are used in a pathway that signals from where to where (the whole extent)? By contrast, how efficient (in terms of number of steps) is the JAK-STAT pathway? (3 points)

membrane to gene, signal transducers and activators of transcription get from then to thar directly

59. Suppose a researcher shows that someone who has age-related macular degeneration (AMD) also has a mutation in the same gene that causes Stargardt's disease. Why might a critic claim that that is not evidence that mutations in this gene cause AMD? (2 points)

need to show that mutant cosegregates with disease especially for such a huge gene

60. What is glycogen synthase kinase-3 (GSK-3) and what does it do? (2 points)

serine threonine kinase marks beta catenin for ubiquitination

61. What residues of what (functional) molecule bind Zn in a Zn-finger so that this molecule can bind what other molecule? (3 points)

amino acids of steroid receptor, and zinc finger grabs DNA

62. Where would you find the hedgehog molecule doing its job, and what is the precursor of this molecule? (2 points)

it's an extracellular ligand, and it is chopped down from a bigger peptide

63. Blindness may be caused by mutations in "rim protien" (thought to be a retinal transporter related to CFTR) and in the cGMP gated channel. Compare the shapes and probable multimeric configurations of these molecules. (2 points)

such a transporter should be a pseudodimer, 2 components in one molecule, would take 2 to make bagel (doughnut), channel is like shaker, it would take 4

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