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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)
sequence exons of gene suspected of being involved
in normal and patient and compare for nucleotide changes

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)
G-protein-coupled receptor
lots (most of receptor diversity may arise from olfactory sense)
the G protein has a specific alpha subunit Golf

3. To (a) what state of (b) what molecule does arrestin bind? (c) Why was arrestin also called S-antigen? (3 points)
to phosphorylated rhodopsin
this small (48 kD) protein is soluable (S) and induces autoimmunity

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)
molecules held together by PDZ-domain INAD protein
molecules diffuse to interact with eachother

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)
SH2 and SH3 (src homology)

6. Why is the ras molecule is localized where it is? (1 point)
a farnesyl transferase puts a fatty acid onto it for membrane localization

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)
It's like PIP with more sugar groups with protein bound to it

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)
too many new blood vessels which leak or bleed
zapping out some retina with a laser decreases angiogenesis signal
invasion of blood vessels into tumor nourishes tumor which is bad

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)
SH2 and pY, JAK phosphorylates tyrosine on STAT
Signal Transducer and Activator of Transcription

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

11. Describe the number and locations of tumors in hereditary and nonhereditary retinoblastoma. (2 points)
hereditary - lots - both eyes, non - 1 - 1 eye

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)
Wnt, wingless
they compete for ligand binding extracellularly

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)
itself or lots of other hormone receptor proteins
1-5 nucleotides between
Zn finger

14. What is a DNA ladder and to what does it apply? (2 points)
electrophoretic pattern of DNA chopped to small lengths in apoptosis

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)
a big enough peptide to have 4 alpha helices
a ligand dimer dimerized the receptor for activation

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)
fish through birds - good, lower mammals pretty iffy
NW-dichromatic, OW & people - trichromatic
diversity of gene and Mary Lyon X-inactivation can make mosaic
retina which can see color
"red" (yellow) and green genes (on X) diverged, many copies, men
are more likely to be color blind than women
18. Describe or draw the cyclic nucleotide gated channel with respect to membrane localization and ligand binding site. (2 points)
The 6 S domains like Shaker, also P between S5 and S6
cGMP binding domain near C terminus on cytoplasmic side

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)
Ca2+ from IP3 signalling to TRP which is SOC for transduction in fly
GCAP's (activating proteins) regulated by Ca2+ for adaptation to regulate
cGMP in rods

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)
involved im progression of morphogenetic furrow
dpp, the TGF-beta homologue

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)
it boots GDP out of ras-GDP

23. What is gusducin? (1 point)
like transducin, but in taste

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)
odd to have a proviral insert in intron 1 plus a point mutation in
exon 7
without PDE functional, cGMP would persist and channel would be open
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)
cholesterol is attached to N-terminal (signalling) HH part to regulate
affinity for membrane
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)
red is really like light, far red reverses that, so R-FR has no effect
and FR-R would be like light pulse

27. What is the current thinking on how ras activates raf? (1 point)
activated ras (ras-GTP) recruits raf to embrane localization

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)
retinoic acid, cellular retinoic acid binding protein (CRABP)

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)
interleukin-1 beta-converting enzyme, a protease

30 In familial adenomatous polyposis coli (APC), an important tumor suppressor is involved. Name one other important molecule in this signalling pathway. (1 point)
Wnt, Frizzled, Dsh, GSK3 (APC) beta-catenin

31. At what step in a signalling pathway (where in the cascade) is Notch? Describe the Notch molecule and its localization. (3 points)
big molecule with one transmembrane domain, lots of EGF repeats and a
few LN repeats extracellularly, PEST and CDC repeats inside

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

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)
a peptide ligand
its receptor is like epithelial sodium channel and C. elegans mechanoreceptive degenerin

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)
KAT has extra amino acids in P, no ball and chain, nucleotide binding
TRP has ankyrin repeats for linkage to Ca2+ cistern

36. What is the difference between vasculogenesis and angiogenesis. Name (an abbreviation will suffice) a ligand involved in one of these processes. (2 points)
vasculogenesis for initial blood vessel formation
angiogenesis for remodeling
VEGF, Ang-1, Ang-2
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)
dauer larva formation
insulin like growth factor receptor

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

39. Responsivities to all-trans vs. 9-cis retinoic acids define what two families of receptors? (2 points)
RAR vs RXR (both with alpha, beta and gamma types)

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)
Rhodopsin:Transducin::10:1, still there is amplification because
activated rhodopsin can activate many transducins by diffusion

41. What is the function of bacteriorhodopsin? (1 point)
pumps proteins (not for vision)

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)
no receptor potential, PLC-beta, cGMP-PDE

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)
it phosphorylates MAP-kinase
in cytoplasm
way downstream from the ligand
44. What is an "orphan" receptor? (1 point)
a receptor for which the ligand is not known

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

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

47. What is the TUNEL technique used for? (1 point)
to see cells dying by apoptosis

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