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Evening Core
Exam 4
April 2, 2008
Name ___________________________
Notes to Students:
1.
Write your name on EACH PAGE. The pages will be separated for grading. If your
name is not on the page and we cannot identify your work you will not receive points
for that page. Please write your name on this page.
2.
Space for each question is provided on the FRONT of the exam pages. You
should not need to use the extra space on the back of the page. However, if you
make a mistake on the front, you may cross it out and write your answer on the back.
3.
Answer completely, but CONCISELY and clearly. One or a few words may be
enough for some questions. Extraneous, unnecessary information will not gain you
points. If the extra information is wrong, then it may cause points to be taken
away. Diagrams, flow charts, and pictures are acceptable in addition to or in lieu of
text.
4.
The points on the exam add up to 96; I will calculate your score as a percentage of the
total points. There are 7 sections (10 pages) on this exam.
1
Evening Core
Exam 4
April 2, 2008
Name ___________________________
Section 1 (Dr. Christophe Depre; 12 points total)
Provide IN ONE SENTENCE a definition for the following. (2 points each)
Importin.
Profilin.
Mitochondrial cristae.
Kinesin.
Nuclear lamina.
Lysosome.
2
Evening Core
Exam 4
April 2, 2008
Name ___________________________
Section 2 (Dr. David DeFouw ; 20 points total)
1.
Microscopic Techniques (10 points)
A recently discovered protein was reported to be a secretory product of cells in either the
kidneys or liver. Describe the microscopic techniques you would use to determine the
cellular source of this new macromolecule.
2.
Membrane Structure (10 points)
Describe the roles of transmembrane and peripheral membrane proteins in the normal
process that results in a biconcave disc shape for mature red blood cells (RBCs). Also
indicate the consequences when RBCs fail to fully mature into this biconcave shape
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Evening Core
Exam 4
April 2, 2008
Name ___________________________
Section 3 (Dr. Carolyn Suzuki; 12 points total)
Question 1. GTP binding and hydrolysis are required for protein translocation into the
endoplasmic reticulum (ER). Describe one step in the translocation process that requires
GTP. (2 points)
Question 2. Ran is the key regulator of nuclear import and export. In words, please answer
the following questions:
A. What is the function of Ran in the IMPORT of proteins into the nucleus?
(2 points)
B. What is the function of Ran in the EXPORT of proteins into the nucleus?
(2 points)
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Evening Core
Exam 4
April 2, 2008
Name ___________________________
Section 3 (Dr. Carolyn Suzuki, continued)
Question 3. The orientation of integral membrane proteins that enter the secretory pathway
is determined by stop-transfer and/or signal anchor sequences. Identify the location of the
polypeptide segments numbered #1, 2, 3 and 4 (for example, lumenal, membrane or
cytosolic). (4 points)
#1 _________
#2 ____________ #3 _______________
#1
#2
#3
#4 _____________
#4
Question 4. List 2 characteristics of protein translocation into the nucleus, which differ from
that into the ER. (2 points)
5
Evening Core
Exam 4
April 2, 2008
Name ___________________________
Section 4 (Dr. David Kaback; 12 points total)
(2 points each)
a. What stage of mitosis is represented in the
diagram on the left?
b. Using an arrow, point to the precise location of the
motor used to propel chromosomes in the direction of
the movement shown.
c. Is this a plus or a minus end motor?
d. This motor has been suggested by immunofluorescence experiments to “jump” from this
location onto the mitotic spindle where it is again used for anaphase B movement.
Using the diagram below and (an) arrow(s), show precisely where this motor is located during
anaphase B movement.
e. Using an arrow labeled “GMT”, show precisely where in this diagram are you most likely to
find a growing microtubules.
f. Using a γ (gamma) show precisely the two locations you are likely to find γ tubulin protein.
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Evening Core
Exam 4
April 2, 2008
Name ___________________________
Section 5 (Dr. Raymond Birge; 10 points total)
1. Members of the epidermal growth factor receptor tyrosine kinase (RTK) family
(EGFR/ERBB1, ERBB2/HER2, ERBB3/HER3 and ERBB4/HER4) are key targets for
inhibition in cancer therapy. Critical for activation is the formation of a dimer in the
cytoplasmic domain that induces autophosphorylation on specific tyrosine residues. A
cytoplasmic protein, called MIG6, interacts with the cytoplasmic domains of RTKs and inhibits
their kinase domain. Based on your knowledge of RTK signaling discussed in class, what
effect would you expect MIG6 overexpression in cancer cells to have on (a) Ras activation,
(b) PI3-kinase activation, and (c) MAP kinase translocation into the nucleus. Briefly explain
your answer. (6 points)
2. Briefly describe two key differences that contrast signaling between receptor tyrosine
kinases (RTKs) and G-protein coupled receptors (GPCRs). (4 points)
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Evening Core
Exam 4
April 2, 2008
Name ___________________________
Section 6 (Dr. Andrew Thomas; 20 points total)
1.
Hormones can bring about changes in cell function by altering gene expression or by
altering the activity of existing proteins by phosphorylation.
1A.
What are the relative advantages of hormone action through phosphorylation and
gene expression? (4 points)
1B.
How can effects of hormones mediated by these two mechanism be undone once the
stimulating hormone is removed? (4 points)
2.
A novel hormone called ghrelin has been identified. It regulates the secretion of
growth hormone from the anterior pituitary. Studies show that ghrelin acts to increase
cytosolic Ca2+ levels in its target pituitary cells. The removal of extracellular Ca2+
does not block the ability of ghrelin to increase cytosolic Ca2+. Treatment of cells with
ghrelin leads to a reduction in the membrane content of phosphatidylinositol-4,5bisphosphate. Ghrelin has been found to bind to a receptor with 7 transmembrane
domains. Answer the following questions about the signaling pathway utilized by
ghrelin:
2A.
Is this pathway likely to involve a G-protein, and if so which one? (2 points)
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Evening Core
Exam 4
April 2, 2008
Name ___________________________
Section 6 (Dr. Andrew Thomas, continued)
2B.
Name the second messenger that most likely leads to the increase in cytosolic Ca2+.
(1 point)
2C.
Describe one mechanism for the removal of the second messenger once the hormone
is removed. (2 points)
2D.
Describe one mechanism that will participate in returning Ca2+ levels to the basal
value after the second messenger has been removed. (2 points)
2E.
Draw a diagram of the pathway that ghrelin acts through, starting with hormone
binding to the receptor and ending with the increase in cytosolic Ca2+. (5 points)
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Evening Core
Exam 4
April 2, 2008
Name ___________________________
Section 7 (Dr. Annie Beuve; 10 points total)
1. Briefly describe three molecular features that distinguish the steroid hormone nuclear
receptors (group I) signaling from the retinoic acid and thyroid nuclear receptors (group II)
signaling. (5 points)
2. Tamoxifen, which has a structure similar to estrogen, is the most used drug to treat breast
cancer. Addition of tamoxifen to cultures of uterine carcinoma cells leads to decrease in
several transcription activators known to induce proliferation. What is a possible target of
this drug? Explain the molecular mechanism of its action. Be specific (5 points).
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