Deck 15: Cell Signaling
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Deck 15: Cell Signaling
1
In the following graphs, the cellular response, as measured in real time by the concentration of a certain active effector protein, is plotted over time for five cell types (A to E) that are treated with three different concentrations of a signal molecule. During the time period indicated by the horizontal gray bar, the signal molecule is present in the culture media at a concentration of 1 nM (dotted curve), 5 nM (gray curve), or 25 nM (solid curve). Answer the following question(s) based on these graphs.
-Which of the cell types A to E shows a response with the highest persistence?
A)
B)
C)
D)
E)
-Which of the cell types A to E shows a response with the highest persistence?
A)

B)

C)

D)

E)

A
2
Whereas the cholera toxin ADP-ribosylates the α subunit of stimulatory G protein (Gs), thereby blocking GTP hydrolysis, pertussis toxin ADP-ribosylates the α subunit of inhibitory G protein (Gᵢ) and prevents interaction with the receptor. What is the effect of these toxins on the concentration of intracellular cAMP?
A) Cholera toxin tends to increase cAMP concentration, whereas pertussis toxin tends to decrease cAMP concentration.
B) Cholera toxin tends to decrease cAMP concentration, whereas pertussis toxin tends to increase cAMP concentration.
C) They both tend to increase cAMP concentration.
D) They both tend to decrease cAMP concentration.
A) Cholera toxin tends to increase cAMP concentration, whereas pertussis toxin tends to decrease cAMP concentration.
B) Cholera toxin tends to decrease cAMP concentration, whereas pertussis toxin tends to increase cAMP concentration.
C) They both tend to increase cAMP concentration.
D) They both tend to decrease cAMP concentration.
C
Explanation: While cholera toxin causes constitutive Gs activation, pertussis toxin prevents Gᵢ activation. Both of these result in a net activation of adenylyl cyclase, leading to higher cAMP levels. Note that adenylyl cyclase is not the only target of Gᵢ.
Explanation: While cholera toxin causes constitutive Gs activation, pertussis toxin prevents Gᵢ activation. Both of these result in a net activation of adenylyl cyclase, leading to higher cAMP levels. Note that adenylyl cyclase is not the only target of Gᵢ.
3
A certain effector protein can be activated by phosphorylation at a key tyrosine residue. An upstream kinase rapidly phosphorylates this tyrosine in the presence of a signal. However, the kinase also phosphorylates and activates a slow-acting phosphatase that can dephosphorylate the phosphotyrosine. Which curve in the following graph would you expect to represent the activity of the effector molecule over time? The input signal is present during the period indicated in gray. The dashed line represents the response in the absence of the phosphatase. 

B
4
The Src kinase can be regulated by at least two mechanisms. Kinases of the CSK family inactivate Src by phosphorylating a C-terminal tyrosine residue. On the other hand, binding of activating ligands (including some activated receptor tyrosine kinases, or RTKs) results in autophosphorylation at a tyrosine residue near the active site, stimulating Src activity. Full activation of Src therefore requires both dephosphorylation at the inhibitory tyrosine and binding to an RTK. Which of the following logic gates (A to E) correctly models the activation of Src kinase (output) as a function of the activity of the upstream regulators (inputs)? 

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5
In which of the following schematic drawings of signaling pathways does the activation of the receptor lead to gene expression? Activating and inhibitory steps are indicated with (+) and (-), respectively. 

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6
Which of the following is NOT a common second messenger in cell signaling?
A) Ca²⁺
B) Cyclic adenosine monophosphate
C) Diacylglycerol
D) Tyrosine
E) Inositol trisphosphate
A) Ca²⁺
B) Cyclic adenosine monophosphate
C) Diacylglycerol
D) Tyrosine
E) Inositol trisphosphate
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7
Indicate true (T) and false (F) statements below regarding G-protein-coupled receptors (GPCRs). Your answer would be a five-letter string composed of letters T and F only, e.g. TTFFF.
( ) All GPCRs share a similar structure composed of seven transmembrane helices.
( ) All GPCR ligands (signal molecules) have a similar structure.
( ) GPCRs have only been found in multicellular organisms, consistent with their role in intercellular signaling.
( ) The hormone insulin is recognized by a GPCR on the surface of its target cells.
( ) Once activated, a GPCR molecule can activate multiple molecules of G protein to amplify the incoming signal.
( ) All GPCRs share a similar structure composed of seven transmembrane helices.
( ) All GPCR ligands (signal molecules) have a similar structure.
( ) GPCRs have only been found in multicellular organisms, consistent with their role in intercellular signaling.
( ) The hormone insulin is recognized by a GPCR on the surface of its target cells.
( ) Once activated, a GPCR molecule can activate multiple molecules of G protein to amplify the incoming signal.
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8
In the following graphs, the cellular response, as measured in real time by the concentration of a certain active effector protein, is plotted over time for five cell types (A to E) that are treated with three different concentrations of a signal molecule. During the time period indicated by the horizontal gray bar, the signal molecule is present in the culture media at a concentration of 1 nM (dotted curve), 5 nM (gray curve), or 25 nM (solid curve). Answer the following question(s) based on these graphs.
-Which of the cell types A to E shows the widest dynamic range of signal concentration?
A)
B)
C)
D)
E)
-Which of the cell types A to E shows the widest dynamic range of signal concentration?
A)

B)

C)

D)

E)

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9
For the α subunit of a trimeric G protein, …
A) a G-protein-coupled receptor (GPCR) acts as a guanine nucleotide exchange factor (GEF), whereas a regulator of G protein signaling (RGS) can act as a GTPase-activating protein (GAP).
B) a GPCR acts as a GAP, whereas an RGS can act as a GEF.
C) both a GPCR and an RGS can act as a GEF.
D) both a GPCR and an RGS can act as a GAP.
A) a G-protein-coupled receptor (GPCR) acts as a guanine nucleotide exchange factor (GEF), whereas a regulator of G protein signaling (RGS) can act as a GTPase-activating protein (GAP).
B) a GPCR acts as a GAP, whereas an RGS can act as a GEF.
C) both a GPCR and an RGS can act as a GEF.
D) both a GPCR and an RGS can act as a GAP.
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10
Consider the signaling pathway depicted below, which involves two different receptors. Assume that a protein is active only when it is activated but not inhibited by its upstream signaling molecules. Activation and inhibition are indicated by normal and blunt arrows, respectively. Under which of the following conditions is target-gene expression induced? 
A) Only in the presence of both signals (1 and 2)
B) In the presence of either or both signals (1 or 2)
C) In the presence of either signal but not both of them
D) Only in the absence of both signals
E) Only in the presence of signal 2 but not signal 1

A) Only in the presence of both signals (1 and 2)
B) In the presence of either or both signals (1 or 2)
C) In the presence of either signal but not both of them
D) Only in the absence of both signals
E) Only in the presence of signal 2 but not signal 1
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11
A cell expresses a transmembrane protein that is cleaved at the plasma membrane to release an extracellular fragment. The fragment binds to receptor proteins on nearby cells and activates signaling pathways resulting in altered gene expression patterns in the cells. What form of intercellular signaling does this represent?
A) Contact-dependent signaling
B) Paracrine signaling
C) Synaptic signaling
D) Endocrine signaling
E) Autocrine signaling
A) Contact-dependent signaling
B) Paracrine signaling
C) Synaptic signaling
D) Endocrine signaling
E) Autocrine signaling
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12
In the following simplified diagram, the activation of a hypothetical allosteric protein is plotted as a function of effector molecule concentration. Which curve (A to E) do you think corresponds to a condition in which activation requires the highest number of effector molecules bound to each protein? 

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13
Cells can adapt to extracellular signal molecules in a variety of ways. Interestingly, exposure to a signal molecule can sometimes not only desensitize the cell to this molecule, but also to one or more other signal molecules that are recognized by different receptors, even if those receptors can still bind to their ligand at the cell surface and initiate signaling. Which subset of the following adaptation mechanisms (for the original signal) can in principle account for this type of desensitization? Choose all that apply. Your answer would be a string composed of letters A to E only, in alphabetical order; e.g. BDE.
(A) Receptor sequestration
(B) Receptor down-regulation
(C) Receptor inactivation
(D) Inactivity of signaling protein
(E) Production of inhibitory protein
(A) Receptor sequestration
(B) Receptor down-regulation
(C) Receptor inactivation
(D) Inactivity of signaling protein
(E) Production of inhibitory protein
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14
Which of the following events normally activates a GTP-binding protein?
A) GTP hydrolysis by the protein
B) Activation of an upstream GTPase-activating protein
C) Activation of an upstream guanine nucleotide exchange factor
D) Phosphorylation of a bound GDP molecule by an upstream phosphorylase
E) Pᵢ release after GTP hydrolysis
A) GTP hydrolysis by the protein
B) Activation of an upstream GTPase-activating protein
C) Activation of an upstream guanine nucleotide exchange factor
D) Phosphorylation of a bound GDP molecule by an upstream phosphorylase
E) Pᵢ release after GTP hydrolysis
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15
In the following graphs, the cellular response, as measured in real time by the concentration of a certain active effector protein, is plotted over time for five cell types (A to E) that are treated with three different concentrations of a signal molecule. During the time period indicated by the horizontal gray bar, the signal molecule is present in the culture media at a concentration of 1 nM (dotted curve), 5 nM (gray curve), or 25 nM (solid curve). Answer the following question(s) based on these graphs.
-Which of the cell types A to E shows the fastest signal adaptation?
A)
B)
C)
D)
E)
-Which of the cell types A to E shows the fastest signal adaptation?
A)

B)

C)

D)

E)

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16
In the following graphs, the cellular response, as measured in real time by the concentration of a certain active effector protein, is plotted over time for five cell types (A to E) that are treated with three different concentrations of a signal molecule. During the time period indicated by the horizontal gray bar, the signal molecule is present in the culture media at a concentration of 1 nM (dotted curve), 5 nM (gray curve), or 25 nM (solid curve). Answer the following question(s) based on these graphs.
-Which of the cell types A to E shows the lowest sensitivity to the signal?
A)
B)
C)
D)
E)
-Which of the cell types A to E shows the lowest sensitivity to the signal?
A)

B)

C)

D)

E)

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17
Consider a signaling protein that can be phosphorylated by a dual-specificity protein kinase at two independent sites (one tyrosine and one serine residue), such that each site is phosphorylated in about 1% of the protein molecules under normal conditions. Phosphorylation at the first site has a short half-life, since a fast tyrosine phosphatase removes the phosphate soon after the residue is phosphorylated, whereas dephosphorylation at the second site-carried out by a serine/threonine phosphatase-is relatively slow. Upon activation of a signaling pathway, the concentration of the dual-specificity kinase increases several-fold rapidly. The phosphorylation state of the tyrosine and serine residues following stimulation is compared in the following graph. Which curve (1 or 2) do you think corresponds to the serine residue? Write down 1 or 2 as your answer.


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18
Which of the following molecular mechanisms is NOT used in the cell in order to produce abrupt responses to a signal?
A) Activation of a protein only when bound to multiple molecules of an activating ligand
B) Activation of a protein only when it is phosphorylated at multiple sites
C) Activation of a protein by simultaneously activating its activator(s) and inactivating its inhibitors
D) A positive feedback loop in which an activated protein positively regulates its activator
E) A negative feedback loop in which an activated protein inhibits its activator without delay
A) Activation of a protein only when bound to multiple molecules of an activating ligand
B) Activation of a protein only when it is phosphorylated at multiple sites
C) Activation of a protein by simultaneously activating its activator(s) and inactivating its inhibitors
D) A positive feedback loop in which an activated protein positively regulates its activator
E) A negative feedback loop in which an activated protein inhibits its activator without delay
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19
You grow a tumor-derived cell line in a suspension culture, in which the cells are seen either as single cells or in cell clusters. The cells have been engineered to express green fluorescent protein (GFP) under the control of the mitogen-activated protein kinase (MAP kinase) pathway. To your culture media, you add different concentrations of fibroblast growth factor (FGF)-which is known to activate the MAP kinase pathway in these cells-and briefly incubate the cells before harvesting them. You also collect, under a microscope, hundreds of individual cell clusters from each suspension. You then disaggregate the cells in all of your samples and use a FACS (fluorescence-activated cell sorting) machine to measure the GFP signal intensity in individual cells. Finally, you plot the results as histograms, as shown below. 
According to these results, which of the following schematic drawings better represents the expression of GFP (a proxy for MAP kinase activation) in the culture after intermediate FGF stimulation? In these drawings, higher GFP expression is represented by a darker shade.


According to these results, which of the following schematic drawings better represents the expression of GFP (a proxy for MAP kinase activation) in the culture after intermediate FGF stimulation? In these drawings, higher GFP expression is represented by a darker shade.

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20
Some signaling pathways in the cell are chiefly based on inhibition rather than activation. For example, proteins that initiate programmed cell death by apoptosis are inhibited by anti-apoptotic proteins, which can in turn be inhibited by a group of pro-apoptotic proteins, and so on. Consider the following networks of inhibitory interactions, in which each protein is inactive if at least one of its inhibitors is active. In which pathway is the activation of either upstream protein (1 or 2) sufficient to inhibit apoptosis? 

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21
Which of the following is a major consequence of activation of phospholipase C-β (PLCβ) by the Gq trimeric GTPase?
A) Elevation of intracellular cAMP levels, leading to the activation of protein kinase A
B) Elevation of PIP₃ levels in the plasma membrane, leading to the activation of protein kinase B
C) Elevation of intracellular Ca²⁺ levels, leading to the activation of protein kinase C
D) Elevation of IP₃ in the plasma membrane, leading to the activation of protein kinase D
E) Elevation of intracellular cGMP levels, leading to the activation of protein kinase G
A) Elevation of intracellular cAMP levels, leading to the activation of protein kinase A
B) Elevation of PIP₃ levels in the plasma membrane, leading to the activation of protein kinase B
C) Elevation of intracellular Ca²⁺ levels, leading to the activation of protein kinase C
D) Elevation of IP₃ in the plasma membrane, leading to the activation of protein kinase D
E) Elevation of intracellular cGMP levels, leading to the activation of protein kinase G
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22
Sort the following events to reflect the normal order in which they occur in G-protein-coupled receptor signaling leading to transcription of genes with cAMP response elements. Your answer would be a four-letter string composed of letters A to E only, e.g. ACBD.
(A) Binding of CREB to PKA
(B) Binding of cAMP to PKA
(C) Dissociation of PKA into catalytic and regulatory subunits
(D) Activation of adenylyl cyclase
(A) Binding of CREB to PKA
(B) Binding of cAMP to PKA
(C) Dissociation of PKA into catalytic and regulatory subunits
(D) Activation of adenylyl cyclase
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23
Fill in the blank in the following paragraph.
"Cytosolic Ca2+ can be sensed by ..., a small, conserved, dumbbell-shaped protein with four Ca2+-binding sites. Upon Ca2+ binding, it binds and activates dozens of proteins by changing its conformation in different ways."
"Cytosolic Ca2+ can be sensed by ..., a small, conserved, dumbbell-shaped protein with four Ca2+-binding sites. Upon Ca2+ binding, it binds and activates dozens of proteins by changing its conformation in different ways."
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24
Genetic screens for enhancers and suppressors of temperature-sensitive loss-of-function mutations in sevenless (sev) in Drosophila melanogaster led to the discovery of some other genes involved in the Ras-MAP-kinase pathway. Would you expect loss-of-function mutations in genes encoding each of the following proteins to be an enhancer (E) or suppressor (S) of sev? An enhancer mutation exacerbates the effect of the original mutation, whereas a suppressor mutation alleviates it. Note that loss-of-function mutations can be just partial defects and not necessarily null mutations. Your answer would be a four-letter string composed of letters E and S only, e.g. EEEE.
( ) Sos
( ) Ras
( ) Ras-GAP
( ) Raf
( ) Sos
( ) Ras
( ) Ras-GAP
( ) Raf
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25
Indicate true (T) and false (F) statements below regarding the Ras-MAP-kinase signaling pathway. Your answer would be a four-letter string composed of letters T and F only, e.g. TTTF.
( ) The immediate early genes turn on a few hours after activation of the RTK.
( ) Ras-GTP binds directly to, and activates, the upstream kinase in the MAP kinase module.
( ) Signal transduction through the Ras-MAP-kinase pathway only leads to a transient response.
( ) In the MAP kinase module, Raf can be phosphorylated by Erk to create a negative feedback loop.
( ) The immediate early genes turn on a few hours after activation of the RTK.
( ) Ras-GTP binds directly to, and activates, the upstream kinase in the MAP kinase module.
( ) Signal transduction through the Ras-MAP-kinase pathway only leads to a transient response.
( ) In the MAP kinase module, Raf can be phosphorylated by Erk to create a negative feedback loop.
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26
What is the effect of using scaffold proteins on precision and amplification capacity in cell signaling?
A) Both precision and amplification are improved.
B) Precision is improved, but amplification is limited.
C) Precision is compromised, but amplification is improved.
D) Both precision and amplification are limited.
A) Both precision and amplification are improved.
B) Precision is improved, but amplification is limited.
C) Precision is compromised, but amplification is improved.
D) Both precision and amplification are limited.
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27
A genetic form of "night blindness" (i.e. poor vision in dim light) is caused by mutations in genes encoding rhodopsin kinase (RK) and arrestin. The mutations reduce the dynamic range of light perception, and the affected individuals have a prolonged light response and adapt very slowly to low light (when entering a dark theater room, for example). Which of the following mutations do you expect to be the cause?
A) Loss-of-function RK mutations and loss-of-function arrestin mutations
B) Loss-of-function RK mutations and gain-of-function arrestin mutations
C) Gain-of-function RK mutations and loss-of-function arrestin mutations
D) Gain-of-function RK mutations and gain-of-function arrestin mutations
A) Loss-of-function RK mutations and loss-of-function arrestin mutations
B) Loss-of-function RK mutations and gain-of-function arrestin mutations
C) Gain-of-function RK mutations and loss-of-function arrestin mutations
D) Gain-of-function RK mutations and gain-of-function arrestin mutations
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28
Indicate true (T) and false (F) statements below regarding the ubiquitin ligase c-Cbl. Your answer would be a four-letter string composed of letters T and F only, e.g. TTTF.
( ) It contains an SH2 domain, and can therefore activate RTK signaling.
( ) It ubiquitylates activated RTKs.
( ) Its overactivation can lead to prolonged RTK signaling and promote the development of cancer.
( ) It is part of a negative feedback loop to down-regulate RTKs.
( ) It contains an SH2 domain, and can therefore activate RTK signaling.
( ) It ubiquitylates activated RTKs.
( ) Its overactivation can lead to prolonged RTK signaling and promote the development of cancer.
( ) It is part of a negative feedback loop to down-regulate RTKs.
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29
Intracellular Ca2+ oscillations, initiated by the activation of IP3 receptors and orchestrated via intricate positive and negative feedback loops, can be subject to frequency modulation, an example of which is the increase in oscillation frequency with increasing stimulus strength. Caffeine is known to bind to and sensitize the ryanodine receptors, resulting in their opening in response to lower calcium ion concentrations. Do you think caffeine would tend to increase (I) or decrease (D) the frequency of calcium ion oscillations in stimulated cells? Write down I or D as your answer.
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30
Consider a signaling protein that is only made up of one SH2 domain and two SH3 domains. This protein is most likely ...
A) a monomeric G protein.
B) a guanine nucleotide exchange factor.
C) a kinase associated with receptor tyrosine kinase signaling.
D) an adaptor protein.
E) a negative regulator of receptor tyrosine kinase signaling.
A) a monomeric G protein.
B) a guanine nucleotide exchange factor.
C) a kinase associated with receptor tyrosine kinase signaling.
D) an adaptor protein.
E) a negative regulator of receptor tyrosine kinase signaling.
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31
In the following schematic diagram showing the initial signaling steps in growth cone collapse in motor neurons, indicate which protein (A to E) corresponds to the following. Your answer would be a four-letter string composed of letters A to E only, e.g. CBAE.
( ) Ephrin
( ) Ephexin
( ) RhoA GTPase
( ) Cytoplasmic tyrosine kinase

( ) Ephrin
( ) Ephexin
( ) RhoA GTPase
( ) Cytoplasmic tyrosine kinase
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32
Indicate whether each of the following descriptions applies to visual signal transduction (V), olfactory signal transduction (O), or both (B). Your answer would be a four-letter string composed of letters V, O, and B only, e.g. VOVV.
( ) It involves cGMP as a second messenger .
( ) A rise in cyclic mononucleotide concentration follows the arrival of the signal.
( ) The signal is received by a G-protein-coupled receptor.
( ) An incoming signal leads to membrane hyperpolarization.
( ) It involves cGMP as a second messenger .
( ) A rise in cyclic mononucleotide concentration follows the arrival of the signal.
( ) The signal is received by a G-protein-coupled receptor.
( ) An incoming signal leads to membrane hyperpolarization.
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33
Which of the following phosphoinositides is the preferred binding target for a PH-domain-containing protein? 

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34
Indicate true (T) and false (F) statements below regarding cellular signaling mediated by nitric oxide (NO). Your answer would be a four-letter string composed of letters T and F only, e.g. TTTF.
( ) Once produced, NO can diffuse to neighboring cells.
( ) NO has known roles in cGMP-independent as well as cGMP-dependent signaling.
( ) NO normally decreases cGMP concentration by activating cGMP phosphodiesterase.
( ) The drug Viagra® counteracts the effects of NO on penile blood vessels.
( ) Once produced, NO can diffuse to neighboring cells.
( ) NO has known roles in cGMP-independent as well as cGMP-dependent signaling.
( ) NO normally decreases cGMP concentration by activating cGMP phosphodiesterase.
( ) The drug Viagra® counteracts the effects of NO on penile blood vessels.
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35
Sort the following events into the order that they take place in phototransduction in response to a flash of light. Your answer would be a four-letter string composed of letters A to E, e.g. BCDEA.
(A) The cGMP level drops.
(B) The cGMP level rises.
(C) The Ca²? level drops.
(D) Retinal isomerizes to an all-trans configuration.
(E) Gt exchanges its bound nucleotide.
(A) The cGMP level drops.
(B) The cGMP level rises.
(C) The Ca²? level drops.
(D) Retinal isomerizes to an all-trans configuration.
(E) Gt exchanges its bound nucleotide.
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36
PI 3-kinase ...
A) is a membrane-associated tyrosine kinase.
B) activates PDK1 by phosphorylating a serine residue on the protein.
C) is counteracted by PTEN phosphatase.
D) is only known to be activated by receptor tyrosine kinases.
E) inhibits Akt.
A) is a membrane-associated tyrosine kinase.
B) activates PDK1 by phosphorylating a serine residue on the protein.
C) is counteracted by PTEN phosphatase.
D) is only known to be activated by receptor tyrosine kinases.
E) inhibits Akt.
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37
What is the major way by which the monomeric G protein Ras is activated in receptor tyrosine kinase signaling?
A) Activation of Ras-GAP
B) Activation of Ras-GEF
C) Inactivation of Ras-GAP
D) Inactivation of Ras-GEF
E) Inactivation of Ras-GDI
A) Activation of Ras-GAP
B) Activation of Ras-GEF
C) Inactivation of Ras-GAP
D) Inactivation of Ras-GEF
E) Inactivation of Ras-GDI
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38
Consider visual transduction in rod photoreceptors in the vertebrate retina. Which of the following steps does NOT normally amplify the signal in this pathway?
A) Activation of transducin by active rhodopsin
B) Blockage of Na⁺ influx by cation-channel closure
C) Cation-channel closure due to cGMP depletion
D) Depletion of cGMP by active cGMP phosphodiesterase
E) All of the above DO involve amplification
A) Activation of transducin by active rhodopsin
B) Blockage of Na⁺ influx by cation-channel closure
C) Cation-channel closure due to cGMP depletion
D) Depletion of cGMP by active cGMP phosphodiesterase
E) All of the above DO involve amplification
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39
Which of the following is NOT part of a negative feedback mechanism in adaptation to light in retinal rod cells?
A) Phosphorylation of G-protein-coupled receptor
B) Binding of arrestin to G protein
C) Stimulation of guanylyl cyclase by decreased Ca²⁺ levels
D) Binding of regulator of G protein signaling to transducin
A) Phosphorylation of G-protein-coupled receptor
B) Binding of arrestin to G protein
C) Stimulation of guanylyl cyclase by decreased Ca²⁺ levels
D) Binding of regulator of G protein signaling to transducin
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40
How is the activation of epidermal growth factor receptor (EGFR) different from that of insulin receptor (IR)?
A) EGFR is a dimer in its inactive and active forms, whereas IR dimerizes only when active.
B) EGFR activation requires dimerization, whereas IR can become activated as a monomer.
C) EGFR is activated by transautophosphorylation, whereas IR activation is phosphorylation-independent and is a simple consequence of receptor dimerization.
D) Unlike IR activation, EGFR activation involves an asymmetric arrangement of the intracellular kinase domains.
E) Both C and D above.
A) EGFR is a dimer in its inactive and active forms, whereas IR dimerizes only when active.
B) EGFR activation requires dimerization, whereas IR can become activated as a monomer.
C) EGFR is activated by transautophosphorylation, whereas IR activation is phosphorylation-independent and is a simple consequence of receptor dimerization.
D) Unlike IR activation, EGFR activation involves an asymmetric arrangement of the intracellular kinase domains.
E) Both C and D above.
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41
Which of the following proteins lacks a PH domain?
A) Sos (a Ras-GEF)
B) Grb2 (an RTK signaling adaptor)
C) Pleckstrin (a protein kinase C substrate)
D) Akt (protein kinase B)
E) PDK1 (phosphoinositide-dependent kinase)
A) Sos (a Ras-GEF)
B) Grb2 (an RTK signaling adaptor)
C) Pleckstrin (a protein kinase C substrate)
D) Akt (protein kinase B)
E) PDK1 (phosphoinositide-dependent kinase)
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42
Indicate whether each of the following occurs inside the cell in the presence (P) or absence (A) of stimulation with a Hedgehog signal. Your answer would be a four-letter string composed of letters P and A only, e.g. PPPP.
( ) Sequestration of Smoothened in intracellular vesicles
( ) Accumulation of unprocessed Ci in the nucleus
( ) Phosphorylation of Smoothened
( ) Recruitment of Fused and Costal2 to the plasma membrane
( ) Sequestration of Smoothened in intracellular vesicles
( ) Accumulation of unprocessed Ci in the nucleus
( ) Phosphorylation of Smoothened
( ) Recruitment of Fused and Costal2 to the plasma membrane
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43
Fill in the blank in the following paragraph regarding plant hormones. DO NOT use abbreviations.
"As simple a signaling molecule as it is, ... is also a key regulator of plant physiology. It can promote processes such as fruit ripening, flower opening, and leaf abscission; it can also be produced in response to various types of stress including drought, flooding, and bacterial and viral infections."
"As simple a signaling molecule as it is, ... is also a key regulator of plant physiology. It can promote processes such as fruit ripening, flower opening, and leaf abscission; it can also be produced in response to various types of stress including drought, flooding, and bacterial and viral infections."
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44
Proteins of the Src family (e.g. Src, Fyn, Lck, and Hck) have important roles in several signaling pathways in mammals. A typical Src family protein ...
A) is a cytosolic tyrosine kinase.
B) contains SH2 and SH3 domains in addition to a kinase domain.
C) has covalently attached lipid chains.
D) is located on the cytoplasmic side of the plasma membrane.
E) All of the above.
A) is a cytosolic tyrosine kinase.
B) contains SH2 and SH3 domains in addition to a kinase domain.
C) has covalently attached lipid chains.
D) is located on the cytoplasmic side of the plasma membrane.
E) All of the above.
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45
Activated STATs can induce the expression of SOCS proteins, which in turn inhibit the JAK-dependent phosphorylation of the STATs. Under sustained serum stimulation of mouse fibroblast cells, a number of oscillations can be observed as a consequence of this delayed negative feedback loop, as shown in the following simplified graph. According to this graph, approximately how long is the delay in the feedback response, and what process is mainly responsible for it? 
A) 1 hour; transcription
B) 2 hours; transcription
C) 1 hour; mRNA export
D) 1 hour; mRNA translation
E) 2 hours; mRNA translation

A) 1 hour; transcription
B) 2 hours; transcription
C) 1 hour; mRNA export
D) 1 hour; mRNA translation
E) 2 hours; mRNA translation
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46
How does the expression of Delta on the surface of a cell activate the expression of certain genes in the nucleus of its neighboring cell?
A) Delta binding activates Notch, which activates a transcriptional activator through the JAK-STAT pathway.
B) Delta binding leads to the stabilization of a cytoskeleton-associated transcriptional activator.
C) Delta binding releases the intracellular tail of Notch, which enters the nucleus and converts a transcriptional repressor into a transcriptional activator.
D) Delta binding leads to Notch-mediated recruitment of protein complexes to the plasma membrane, resulting in the degradation of a transcriptional repressor.
E) Delta binding leads to the proteolytic cleavage of Notch and inhibition of its activity as a transcriptional repressor, leading to the activation of target genes.
A) Delta binding activates Notch, which activates a transcriptional activator through the JAK-STAT pathway.
B) Delta binding leads to the stabilization of a cytoskeleton-associated transcriptional activator.
C) Delta binding releases the intracellular tail of Notch, which enters the nucleus and converts a transcriptional repressor into a transcriptional activator.
D) Delta binding leads to Notch-mediated recruitment of protein complexes to the plasma membrane, resulting in the degradation of a transcriptional repressor.
E) Delta binding leads to the proteolytic cleavage of Notch and inhibition of its activity as a transcriptional repressor, leading to the activation of target genes.
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47
Indicate true (T) and false (F) statements below regarding signaling in plants. Your answer would be a four-letter string composed of letters T and F only, e.g. TTTF.
( ) Since multicellularity evolved before the divergence of the plant and animal lineages, plants have homologs of most animal signaling proteins, such as nuclear receptors, Ras, JAK, and Notch.
( ) Receptor tyrosine kinases are the largest class of cell-surface receptors in plant cells.
( ) Both plants and animals use cyclic GMP, NO, and Ca²? for cell signaling.
( ) Leucine-rich repeat (LLR) receptor kinases are the most abundant type of receptor serine/threonine kinases in plants.
( ) Since multicellularity evolved before the divergence of the plant and animal lineages, plants have homologs of most animal signaling proteins, such as nuclear receptors, Ras, JAK, and Notch.
( ) Receptor tyrosine kinases are the largest class of cell-surface receptors in plant cells.
( ) Both plants and animals use cyclic GMP, NO, and Ca²? for cell signaling.
( ) Leucine-rich repeat (LLR) receptor kinases are the most abundant type of receptor serine/threonine kinases in plants.
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48
You have studied the circadian clock in a certain mouse strain by monitoring the physical activity (e.g. wheel-running) of a few mice over an extended period of time. For the first week, you kept the mice under normal 12 hr light /12 hr dark cycles; they were then transferred to constant darkness. You have plotted the average activity of the mice in the following graph. The light and dark conditions are represented with white and gray backgrounds, respectively. The activity in each day is plotted in black in one row of the graph, and consecutive days are arranged from the top to the bottom. The horizontal axis represents the time of the day. Based on these results, what is the most accurate estimate for the free-running period of the circadian clock in this mouse strain? 
A) About 25 hr
B) About 24.5 hr
C) About 24 hr
D) About 23.5 hr
E) About 23 hr

A) About 25 hr
B) About 24.5 hr
C) About 24 hr
D) About 23.5 hr
E) About 23 hr
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49
All nuclear receptors ...
A) are cytosolic proteins that enter the nucleus upon ligand binding.
B) have ligand-binding and DNA-binding domains, and can directly bind to DNA.
C) are transcriptional activators when bound to their ligand.
D) bind to steroid hormones.
E) are transcriptional repressors in the absence of their ligand.
A) are cytosolic proteins that enter the nucleus upon ligand binding.
B) have ligand-binding and DNA-binding domains, and can directly bind to DNA.
C) are transcriptional activators when bound to their ligand.
D) bind to steroid hormones.
E) are transcriptional repressors in the absence of their ligand.
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50
The phosphorylation state of a human protein follows the oscillatory pattern shown in the first graph below. The protein is phosphorylated by two kinases (1 and 2), both of which are activated in an oscillatory pattern. Kinase 1 oscillates in congruence with the circadian rhythm, while kinase 2 oscillates at a higher frequency and is independent of the circadian clock. The second graph shows the phosphorylation state of the same protein in mutant cells lacking one of the kinases mentioned above. Which kinase (1 or 2) do you think is missing in these mutant cells? Write down 1 or 2 as your answer.


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51
In the following simplified diagram of the NF?B-dependent signaling pathway, indicate which boxes (A to C) correspond to the NF-?B, I?B, and IKK proteins, respectively. Your answer would be a three-letter string composed of letters A to C only, e.g. BCA.


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52
What two cell-surface receptors are represented in the two simplified diagrams below (from left to right)? 
A) TGFβ receptor and TNF receptor.
B) Cytokine receptor and TNF receptor.
C) TNF receptor and TGFβ receptor.
D) TGFβ receptor and cytokine receptor.
E) Cytokine receptor and TGFβ receptor.

A) TGFβ receptor and TNF receptor.
B) Cytokine receptor and TNF receptor.
C) TNF receptor and TGFβ receptor.
D) TGFβ receptor and cytokine receptor.
E) Cytokine receptor and TGFβ receptor.
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53
Indicate true (T) and false (F) statements below regarding the mTOR complexes. Your answer would be a four-letter string composed of letters T and F only, e.g. TTTF.
( ) mTOR in complex 1 contains the protein raptor, is sensitive to rapamycin, and stimulates cell growth.
( ) Akt activation is stimulated by mTOR in complex 2, which contains the protein rictor.
( ) Akt activates mTOR in complex 2 by activating a Rheb-GAP called Tsc2.
( ) mTOR in complex 1 is activated in the presence of growth factors.
( ) mTOR in complex 1 contains the protein raptor, is sensitive to rapamycin, and stimulates cell growth.
( ) Akt activation is stimulated by mTOR in complex 2, which contains the protein rictor.
( ) Akt activates mTOR in complex 2 by activating a Rheb-GAP called Tsc2.
( ) mTOR in complex 1 is activated in the presence of growth factors.
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54
In the following diagram showing five parallel signaling pathways downstream of a receptor tyrosine kinase (RTK) and a G-protein-coupled receptor (GPCR), indicate which boxes (A to E) correspond to the following proteins. Your answer would be a five-letter string composed of letters A to E only, e.g. CDBAE.
( ) Cyclic AMP
( ) Protein kinase C
( ) Sos
( ) PI(3,4,5)P3
( ) Ca2+

( ) Cyclic AMP
( ) Protein kinase C
( ) Sos
( ) PI(3,4,5)P3
( ) Ca2+
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55
Cancer-related genes can be classified into two major groups. Proto-oncogenes encode proteins that normally act in promoting cell growth and proliferation. Gain-of-function mutations in proto-oncogenes can therefore transform the cells into a cancerous state. Tumor suppressor genes, on the other hand, encode proteins that normally function to keep cell proliferation in check. Thus, loss-of-function mutations in tumor suppressors can lead to cancer by eliminating the inhibitory effect of these genes. Mutations in genes encoding the components of the canonical Wnt signaling pathway are commonly found in colorectal tumors. Indicate whether the gene for each of the following is a proto-oncogene (P) or tumor suppressor (T). Your answer would be a four-letter string composed of letters P and T only, e.g. PPPP.
( ) Wnt
( ) APC
( ) Axin
( ) ?-Catenin
( ) Wnt
( ) APC
( ) Axin
( ) ?-Catenin
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56
The SH2 domain of STAT proteins plays a key role in cytokine receptor signaling. This domain can bind to phosphotyrosine ...
A) on an activated receptor molecule, or (intramolecularly) on the same STAT molecule.
B) on a Janus kinase molecule, or (intramolecularly) on the same STAT molecule.
C) on an activated receptor molecule, or on another STAT molecule in a dimer.
D) on a Janus kinase molecule, or on another STAT molecule in a dimer.
E) on the same STAT molecule or on another STAT molecule in a dimer.
A) on an activated receptor molecule, or (intramolecularly) on the same STAT molecule.
B) on a Janus kinase molecule, or (intramolecularly) on the same STAT molecule.
C) on an activated receptor molecule, or on another STAT molecule in a dimer.
D) on a Janus kinase molecule, or on another STAT molecule in a dimer.
E) on the same STAT molecule or on another STAT molecule in a dimer.
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57
Ethylene receptors in plant cells ...
A) are located primarily at the plasma membrane.
B) are single-pass transmembrane proteins.
C) interact with CTR1, which is closely related to the monomeric G protein Ras.
D) have a copper-containing ethylene-binding domain.
E) All of the above.
A) are located primarily at the plasma membrane.
B) are single-pass transmembrane proteins.
C) interact with CTR1, which is closely related to the monomeric G protein Ras.
D) have a copper-containing ethylene-binding domain.
E) All of the above.
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58
Regulation of the Ci (Cubitus interruptus) protein in the Hedgehog signaling pathway is reminiscent of that of β-catenin in the Wnt pathway. Which of the following features is shared among these two proteins?
A) Both proteins are ubiquitylated when the signal (Hedgehog or Wnt) is present.
B) Both proteins are able to enter the nucleus only in the absence of the signal.
C) Both proteins can be phosphorylated by GSK3 and CK1 in the absence of the signal.
D) Both proteins are fully degraded by the proteasome in the absence of the signal.
E) None of the above.
A) Both proteins are ubiquitylated when the signal (Hedgehog or Wnt) is present.
B) Both proteins are able to enter the nucleus only in the absence of the signal.
C) Both proteins can be phosphorylated by GSK3 and CK1 in the absence of the signal.
D) Both proteins are fully degraded by the proteasome in the absence of the signal.
E) None of the above.
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59
Which of the following represents the active form of β-catenin in cells stimulated with Wnt?
A) Phosphorylated by GSK3 and CK1
B) Bound to APC
C) Bound to Groucho
D) Bound to LRP
E) None of the above
A) Phosphorylated by GSK3 and CK1
B) Bound to APC
C) Bound to Groucho
D) Bound to LRP
E) None of the above
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60
Which of the following mechanisms is NOT employed by I-Smads to negatively regulate Smad signaling?
A) Competing with R-Smads for binding sites on the receptor, decreasing R-Smad phosphorylation.
B) Recruiting the ubiquitin ligase Smurf, leading to receptor degradation.
C) Binding to caveolin, inhibiting the formation of caveolae.
D) Binding to the co-Smad, Smad4, inhibiting it.
E) Recruiting protein phosphatases, leading to receptor inactivation.
A) Competing with R-Smads for binding sites on the receptor, decreasing R-Smad phosphorylation.
B) Recruiting the ubiquitin ligase Smurf, leading to receptor degradation.
C) Binding to caveolin, inhibiting the formation of caveolae.
D) Binding to the co-Smad, Smad4, inhibiting it.
E) Recruiting protein phosphatases, leading to receptor inactivation.
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61
Indicate whether each of the following descriptions better applies to phytochromes (P), cryptochromes (C), or phototropins (T). Your answer would be a four-letter string composed of letters P, C, and T only, e.g. TPCC.
( ) They respond to red light.
( ) They are found in animals as well as in plants.
( ) They are flavoproteins.
( ) They are dimeric, cytosolic serine/threonine protein kinases that are normally activated by autophosphorylation.
( ) They respond to red light.
( ) They are found in animals as well as in plants.
( ) They are flavoproteins.
( ) They are dimeric, cytosolic serine/threonine protein kinases that are normally activated by autophosphorylation.
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62
Arabidopsis thaliana seedlings show positive phototropism: they bend and grow toward the source of (blue) light. However, phototropism is not observed if the seedlings are treated with an auxin efflux inhibitor called NPA. Knowing that auxin stimulates elongation of the cells in the growing shoot, these observations are consistent with a model in which, in the presence of a lateral light, ...
A) auxin efflux transporter proteins become localized to the side of the cell that is facing the light source.
B) auxin efflux transporter proteins become localized to the side of the cell that is away from the light source.
C) auxin influx transporter proteins become localized to the side of the cell that is facing the light source.
D) auxin influx transporter proteins become localized to the side of the cell that is away from the light source.
E) auxin efflux transporter proteins become uniformly distributed around the cell.
Answers
A) auxin efflux transporter proteins become localized to the side of the cell that is facing the light source.
B) auxin efflux transporter proteins become localized to the side of the cell that is away from the light source.
C) auxin influx transporter proteins become localized to the side of the cell that is facing the light source.
D) auxin influx transporter proteins become localized to the side of the cell that is away from the light source.
E) auxin efflux transporter proteins become uniformly distributed around the cell.
Answers
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63
In the following schematic diagrams of ethylene signaling in plants, 1 denotes ethylene, 2 denotes ethylene receptor, 3 denotes CTR1, 4 denotes EIN3, and 5 represents the expression of ethylene-responsive genes. Which diagram better depicts the signaling pathway? Activation and inhibition are indicated as normal and blunt arrows, respectively. 

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