W23 D103 Final

What are the functions of a cyclin during the cell cycle? (Select all that apply) 1. Activate a CDK 2. Direct a CDK to its targets. 3. Inhibit a CDK. 4. Control CDK activity through phosphorylation of the cyclin. 5. Control CDK activity through synthesis and destruction of the cyclin.

1, 2, and 5

What can an arrestin do to a GPCR? (Select all that apply) A. An arrestin can bind to the GPCR and partially inhibit its signaling. B. An arrestin can stimulate a GRK to phosphorylate the GPCR. C. An arrestin can stimulate endocytosis of the GPCR D. An arrestin can activate MAPK signaling. E. An arrestin can sensitize a GPCR to increase its signaling strength.

A, C, and D

What do the terms "asynchronous" and "synchronous" mean when used to refer to a population of cells going through the cell cycle? A. 'Synchronous' means all cells in the population are at the same stage of the cell cycle at any one time, while 'asynchronous' means the cells in the population are at random stages of the cell cycle. B. 'Asynchronous' means all cells in the population are at the same stage of the cell cycle at any one time, while 'synchronous' means the cells in the population are at random stages of the cell cycle. C. 'Synchronous' means cells in the population spend the same amount of time at each stage of the cell cycle, while 'asynchronous' means the cells spend different amounts of time at each stage of the cell cycle. D. 'Synchronous' means cells in the population are at different stages of the cell cycle at any one time, while 'asynchronous' means the cells in the population are all arrested in the cell cycle.

A. 'Synchronous' means all cells in the population are at the same stage of the cell cycle at any one time, while 'asynchronous' means the cells in the population are at random stages of the cell cycle.

Which of the following mutations would be likely to produce S. pombe cells that are elongated and which require a long time to complete mitosis? A. A mutation that abolishes Cdc25 activity. B. A mutation that increases activity of Cdc25. C. A mutation that increases activity of CAK. D. A mutation in CDK that prevents it from being phosphorylated by Wee1. E. A mutation that abolishes Wee1 activity.

A. A mutation that abolishes Cdc25 activity.

Which domains would you expect to find in an adaptor signaling protein capable of simultaneously binding to (i) a phospho-tyrosine; (ii) a phosphatidyl-inositol (3,4,5) tri-phosphate (PI(3,4,5)P3) and (iii) a di-acyl glycerol (DAG)? A. A protein containing a SH2, a C1 and a PH domain. B. A protein containing a SH3, a Tubby and a C1 domain. C. A protein containing a SH2, a FYVE and a PH domain. D. A protein containing a FYVE, a 14-3-3, and a SH2 domain. E. A protein containing a C1, a FYVE and a WW domain.

A. A protein containing a SH2, a C1 and a PH domain.

Molecule "X" is a second messenger, whose lifespan in cells is 1 min. Following stimulation of a cell surface receptor, production of X decreases one hundred fold. A decrease in concentration of X is required to mediate an increase in the activity of enzyme "Y". What best describes the effect on this signaling pathway if the lifespan of X was 15 min? A. Activity of Y will increase more slowly. B. Activity of Y will decrease more rapidly. C. Activity of Y will decrease more slowly. D. Activity of Y will increase more rapidly. E. Activity of Y will remain unnchanged.

A. Activity of Y will increase more slowly.

How are cohesins removed from the arms of sister chromatids prior to metaphase in mitosis? A. By action of a kinase. B. By action of securin. C. By action of separase. D. Cohesins are not removed from the arms of sister chromatids until anaphaseA during mitosis. E. By action of a phosphatase.

A. By action of a kinase.

Which of the following statements is false? A. Cleavage of PIP2 produces two independent hydrophobic second messengers. B. Viagra is an inhibitor of cGMP phosphodiesterase, which can affect vision. C. IP3 can be phosphorylated to produce IP4. D. Ca 2+ and DAG each bind to and help activate PKC. E. Diacylglycerol (DAG) can translocate in the inner leaflet of the lipid bilayer.

A. Cleavage of PIP2 produces two independent hydrophobic second messengers.

Which of the following effects is least likely to be mediated by a scaffolding protein? A. Decrease specificity of interactions between intracellular signaling proteins. B. Decrease likelihood of crosstalk between signaling pathways that share a common kinase. C. Allow rapid negative feedback of a signaling response. D. Increase the local concentration of signaling components.

A. Decrease specificity of interactions between intracellular signaling proteins.

Which of the following events is required to form a pre-replicative complex in preparation for DNA replication? A. Dephosphorylation of ORC, Cdc6 and Cdt1 during M-phase. B. DNA polymerase function during G1. C. Activity of M-cyclins during S-phase. D. Phosphorylation of ORC, Cdc6 and Cdt1 during S-phase. E. Binding of Cdt1 and Cdc6 to each other during G1.

A. Dephosphorylation of ORC, Cdc6 and Cdt1 during M-phase.

Compared to normal cells, which of the following signalling events would be altered in a human male tissue culture cell line in which the gene encoding the androgen receptor contained a missense mutation that abolishes the receptor's DNA binding activity? A. Genomic, but not non-genomic responses would be affected following addition of testosterone to a tissue culture dish containing the cells. B. Non-genomic, but not genomic responses would be affected following addition of testosterone to a tissue culture dish containing the cells. C. Both genomic and non-genomic responses would be affected following addition of testosterone to a tissue culture dish containing the cells. D. The mutated androgen receptor would be present in the nucleus in the absence of ligand.

A. Genomic, but not non-genomic responses would be affected following addition of testosterone to a tissue culture dish containing the cells.

Which of the following changes in enzyme activity could produce the strongest effect on vasodilation? A. Increase guanylyl cyclase and decrease cGMP phosphodiesterase. B. Increase both guanylyl cyclase and cGMP phosphodiesterase. C. Decrease guanylyl cyclase and increase cGMP phosphodiesterase. D. Decrease both guanylyl cyclase and cGMP phosphodiesterase

A. Increase guanylyl cyclase and decrease cGMP phosphodiesterase.

Which of the following is not an outcome of binding of an arrestin molecule to the cytoplasmic domain of an activated GPCR? A. Increased heterotrimeric GTPase-based signaling by the GPCR. B. Decreased signaling due to temporary endocytosis of the receptor. C. Altered signaling via the GPCR due to activation of new downstream signaling pathways. D. Decreased signaling by the GPCR due to endocytosis and destruction of the receptor. E. All of the above are outcomes of binding of an arrestin molecule to the cytoplasmic domain of an activated GPCR.

A. Increased heterotrimeric GTPase-based signaling by the GPCR.

Which of the following changes occur after phosphorylation of a protein on tyrosine amino acids? A. Increased molecular weight, increased acidity and possible interaction with a SH2 domain-containing protein B. Increased molecular weight, decreased acidity and possible interaction with a SH2 domain-containing protein C. Increased molecular weight, decreased acidity and reduced likelihood of interaction with a SH2 domain-containing protein D. Increased molecular weight, no change in charge and possible interaction with a SH2 domain-containing protein E. Increased molecular weight, increased acidity and reduced likelihood of interaction with a SH2 domain-containing protein

A. Increased molecular weight, increased acidity and possible interaction with a SH2 domain-containing protein

Suppressor of Cytokine Signaling (SOCS) proteins negatively regulate cytokine signaling by recruiting ubiquitin E3 ligases to the cytokine receptor. Which protein performs a similar function in signaling via TGF-beta / BMP receptors? A. Smad7, an I-Smad B. Smad4, a Co-Smad C. Ski D. SnoN E. Smurf1 or 2, Ubiquitin E3 ligases.

A. Smad7, an I-Smad

Which of the following statements is false? A. The alpha subunit of a heterotrimeric GTPase always conveys the signal from a GPCR. B. Many clinically marketed drugs target GPCR signaling systems. C. Bacterial infections can cause life-threatening disease that results from abnormal function of GPCR's. D. Hydrolysis of GTP by a heterotrimeric GTPase subunit can be influenced by interaction of the GTPase and its target protein. E. None of the statements is false

A. The alpha subunit of a heterotrimeric GTPase always conveys the signal from a GPCR.

Which of the following statements is incorrect? A. The beta/gamma subunit of a heterotrimeric GTPase determines the duration of opening of a potassium ion channel. B. Some heterotrimeric GTPases activate adenylyl cyclase while others inhibit it. C. The alpha and gamma subunits of a heterotrimeric GTPase have a post-translational modification. D. In a healthy cell, the concentration of GTP in the cytoplasm is much greater than the concentration of GDP. E. An endocytosed GPCR can be degraded in the lysosome or returned to the cell surface.

A. The beta/gamma subunit of a heterotrimeric GTPase determines the duration of opening of a potassium ion channel.

Which event is required for cell cycle arrest following DNA damage involving double-strand breaks? A. Transcription of a CKI. B. Dephosphorylation of p53. C. Destruction of cyclins by ubiquitination. D. Binding of MDM2 to p53. E. Inhibition of ATM/ATR kinases.

A. Transcription of a CKI.

You are an undergraduate Learning Assistant (LA) that is helping to instruct D103 to your fellow students. You know from experience that real-world analogies can be helpful in remembering how a biological process is controlled. You and your teaching buddies need to develop a real-world analogy to explain how activation of mitotic cyclins and CDK's is controlled as a cell prepares for then enters mitosis. You decide to choose a car as a way to relate to M-Cyclin / CDK and decide to use (i) the ignition switch; (ii) the accelerator pedal and (iii) the brake pedal to explain the function of the key regulatory proteins that control M-cyclin / CDK activity. Using this analogy, which protein's function would equate to the brake pedal? A. Wee1 B. a CKI C. Cdc25 D. CAK

A. Wee1

Molecule "M" is a second messenger, whose lifespan in cells is 1 min. After stimulation of a cell surface receptor, production of M is reduced ten-fold. A decrease in concentration of M is required to mediate an increase in the activity of enzyme "E". What best describes the effect on this signaling pathway if the lifespan of "M" was suddenly changed to 100 min? A. Activity E will decrease more rapidly. B. Activity E will increase more slowly. C. There will be no significant effect. D. Activity E will decrease more slowly. E. Activity E will increase more rapidly.

B. Activity E will increase more slowly.

Which of the following is a mechanism that helps to end an IP3 -mediated Ca 2+ response? A. Delaying phosphorylation of IP3 B. Adding a phosphate to IP3 C. Converting IP3 to DAG D. Pumping Ca 2+ into the cytoplasm. E. Increasing synthesis of PIP2

B. Adding a phosphate to IP3

Which of the following statements is true? A. Thyroid hormone receptors are located in the cytosol until they bind to a ligand. B. An androgen receptor that lacks a DNA binding domain can still signal. C. Unlike the androgen receptor, the retinoic acid receptor (RAR) does not bind a co-activator protein. D. A retinoid hormone receptor lacking a ligand binding domain would be unable to regulate gene expression.

B. An androgen receptor that lacks a DNA binding domain can still signal.

Which best explains why different types of cells might respond to the same extra-cellular signaling molecule in a different manner? A. Because cells can vary in the length of their cell cycle. B. Because different types of cells can have different signaling machinery components. C. Because the core-signaling pathway is similar in all cell types. D. Because different cell types bind extra-cellular signaling molecules in the different manner. E. Because the genome sequence can vary between cells.

B. Because different types of cells can have different signaling machinery components.

Which of the following could decrease signaling via phospholipase C? A. Release of Ca2+ into the cytosol B. Dephosphorylation of IP3 C. Increased synthesis of DAG D. Opening of TRP or Orai1 Ca2+ channels E. Decreased synthesis of IP3 kinase

B. Dephosphorylation of IP3

What is the receptor for nitric oxide (NO) in blood vessels? A. Guanylyl cyclase in endothelial cells. B. Guanylyl cyclase in smooth muscle cells. C. Cyclic GMP in smooth muscle cells. D. Calmodulin in endothelial cells. E. Nitric oxide synthase in endothelial cells.

B. Guanylyl cyclase in smooth muscle cells.

What directly causes the G-alpha subunit of a heterotrimeric GTPase to release its GDP? A. Binding of hormone to the GTPase B. Interaction of the G-alpha subunit with a ligand-bound GPCR C. Separation of the G-beta/gamma subunits from the alpha-subunit. D. Binding of the G-alpha subunit to an effector protein. E. A conformational change in the G-beta/gamma subunits.

B. Interaction of the G-alpha subunit with a ligand-bound GPCR

In your molecular biology class you make two different cDNAs. The first cDNA expresses a green fluorescence protein (GFP) fused to the retinoid hormone receptor. The second cDNA expresses a red fluorescent protein (RFP) fused to the glucocorticoid receptor. You express both cDNA's in the same mammalian cell in a dish and you examine their appearance using a microscope equipped with fluorescence optics. You then add retinoid and glucocorticoid ligands to the dish and wait for 30 min before re-examining the cells. Which colors would be seen in the nucleus and the cytosol before and after addition of the ligands? A. Red and green fluorescence in cytoplasm, but not nucleus before addition of ligands; red and green fluorescence in nucleus after addition of ligands. B. Red fluorescence in cytoplasm and green fluorescence in nucleus before addition of ligands; red and green fluorescence in nucleus after addition of ligands. C. Red and green fluorescence in nucleus before and after addition of ligands. D. Red and green fluorescence in cytoplasm before and after addition of ligands. E. Green fluorescence in cytoplasm and red fluorescence in nucleus before addition of ligands; red and green fluorescence in nucleus after addition of ligands.

B. Red fluorescence in cytoplasm and green fluorescence in nucleus before addition of ligands; red and green fluorescence in nucleus after addition of ligands.

Which of the following list the order of events occurring during a signaling event? A. Stimulus, transduction, receptor, effector, response. B. Stimulus, receptor, transduction, effector, response. C. Stimulus, receptor, effector, transduction, response. D. Stimulus, response, transduction, effector.

B. Stimulus, receptor, transduction, effector, response.

Guanine nucleotide exchange factors (GEFs) activate monomeric GTPases. Which molecule performs the equivalent function for hetero-trimeric GTPases? A. The beta and gamma subunits of the GTPase B. The GPCR C. The GAP D. The target of the alpha subunit of the GTPase E. GDP

B. The GPCR

Which statement is incorrect? A. The lifetime of an intracellular signaling molecule must be short for the cell to be able to cause a relatively large change in the concentration of the signaling molecule in a rapid manner. B. The amino acid sequence of PKA is more closely related to PKC than to PKG. C. Components of intracellular signaling pathways can be small molecules, proteins or lipids. D. Negative feedback systems play important roles in regulating cellular signaling. E. Second messengers can convey a signal via a change in their steady state level.

B. The amino acid sequence of PKA is more closely related to PKC than to PKG.

What happens if a cell is unable to destroy M-cyclin at the end of a cell cycle? A. The cell will complete mitosis but will not be able to activate G1 cyclins during the following cell cycle. B. The cell will be unable to complete mitosis. C. The cell will complete mitosis early. D. The cell will be unable to enter mitosis. E. The cell will fail to disassemble its nuclear membrane.

B. The cell will be unable to complete mitosis.

You have discovered a new gene that encodes an unusual regulatory subunit of PKA, which you name Ro. As with the R2C2 version of PKA, Ro forms a dimer and interacts with two molecules of the same catalytic subunit (C) found in PKA to form a Ro2C2 heterotetramer. However, unlike the R in conventional PKA, each Ro subunit binds 8 molecules of cAMP. Which of the following properties would you predict Ro2C2 PKA would display compared to the conventional R2C2 form of PKA? A. Full activity of PKA with Ro subunits would occur at a higher concentration of cAMP. B. The dynamic range of activity of PKA with Ro subunits would occur over a narrower range of cAMP concentration. C. PKA with Ro subunits would become active at a lower concentration of cAMP. D. The dynamic range of activity of PKA with Ro subunits would over a wider range of cAMP concentration.

B. The dynamic range of activity of PKA with Ro subunits would occur over a narrower range of cAMP concentration.

You are working in a lab as a Bio199 student studying the function of a novel gene that encodes a cell surface transmembrane receptor in Drosophila. Drosophila mutants that lose the function of this receptor show dramatic developmental defects involving loss of legs. Your boss asks you to start analyzing the mouse version of the gene encoding the related cell surface receptor. What might you discover when you undertake this task? A. The mouse genome doesn't appear to have a gene that can encode a protein related to the receptor found in Drosophila B. The mouse genome has several genes whose exon coding sequence different slightly from each other, but each gene is predicted to encode a receptor that is similar to the receptor found in Drosophila C. The mouse genome appears to also have only one gene encoding the transmembrane receptor and its amino acid sequence is identical

B. The mouse genome has several genes whose exon coding sequence different slightly from each other, but each gene is predicted to encode a receptor that is similar to the receptor found in Drosophila

Which of the following statements concerning the cellular machinery that controls the cell cycle is false? (Select all that apply) A. The concentration of cyclins change during the cell cycle, while CDK remains relatively stable. B. M-cyclin / CDK must be inactivated before the cell can complete mitosis. C. CDK's become fully active upon binding a cyclin. D. Both G1-CDK and G1/S-CDK can phosphorylate Rb. E. The major function of active G1-CDK is to transcribe G1/S-cyclins.

C and E

Which of the following types of proteins interacts with and thereby activates Ras? A. A kinase B. A phosphatase C. A GEF D. A GAP E. A GTPase

C. A GEF

Guanine nucleotide exchange factors (GEFs) activate monomeric GTPases. Which of thefollowing might function as a dominant negative GEF? A. A GEF that is unable to bind a guanosine nucleotide. B. A GEF that is unable to interact with its target GTPase. C. A GEF that can bind to a GTPase, but causes an abnormal change in the shape of the GTPase. D. A GEF that bind to a GAP, but not to a GTPase

C. A GEF that can bind to a GTPase, but causes an abnormal change in the shape of the GTPase.

The most abundant source of Ca2+ within a cell is found within the lumen of the ER. During certain signaling events, the second messenger inositol 1,4,5-triphosphate (IP3) can trigger release of Ca2+ from the lumen of the ER into the cytosol. Subsequently, the cell must restore the Ca2+ concentration within the ER lumen in preparation for the next IP3-mediated signaling event. How does the cell "sense" that the ER-lumenal concentration of Ca2+ has decreased? A. A decrease in Ca2+ within the lumen of the ER causes ER Ca2+ store pumps to move Ca2+ back into the lumen of the ER. B. An increase in Ca2+ within the cytoplasm induces a conformational change in calmodulin, which activates pumps that pump calcium out of the cell. C. A decrease in Ca2+ within the lumen of the ER causes a conformational change in an EF hand domain located within the lumen of the ER. D. An increase of Ca2+ within the cytoplasm causes Orai1 calcium channels within the plasma membrane to oligomerize.

C. A decrease in Ca2+ within the lumen of the ER causes a conformational change in an EF hand domain located within the lumen of the ER.

Which of the following molecular mechanisms is NOT used by a cell in order to produce a relatively abrupt response to a signal? A. Activation of a protein by simultaneously activating its activator(s) and inactivating its inhibitors. B. Activation of a protein only when bound to multiple molecules of an activating ligand. C. A feed-forward loop in which production of two proteins is requried to produce an output. D. A positive feedback loop in which an activated protein positively regulates its activator.

C. A feed-forward loop in which production of two proteins is required to produce an output.

Which of the following events normally activates a GDP-bound GTPase? 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 kinase E. Pi release after GTP hydrolysis

C. Activation of an upstream guanine nucleotide exchange factor

Why would nitric oxide be a poor endocrine signaling molecule? A. Because it is only synthesized by a few cell types. B. Because it would be taken up by all cell types due to the fact that it does not need a cell surface receptor. C. Because it has a very short lifetime. D. Because it would only be synthesized in cells containing arginine

C. Because it has a very short lifetime.

Based on your knowledge of cellular signaling you are asked to develop a strategy to boost the concentration of red blood cells (erythrocytes) in cancer patients. Which of the following combinations of changes in activity of targets might produce the best strategy? A. Increase activity of SOCS proteins; decrease activity of Epo receptor; increase activity of SHP1 phosphatase. B. Decrease activity of SOCS proteins; increase activity of Epo receptor; increase activity of SHP1 phosphatase. C. Decrease activity of SOCS proteins; increase activity of Epo receptor; decrease activity of SHP1 phosphatase. D. Decrease activity of SOCS proteins; decrease activity of Epo receptor; decrease activity of SHP1 phosphatase. E. Increase activity of SOCS proteins; increase activity of Epo receptor; increase activity of SHP1 phosphatase

C. Decrease activity of SOCS proteins; increase activity of Epo receptor; decrease activity ofSHP1 phosphatase.

Which of the following is an early consequence of activation of phospholipase C-β (PLCβ) by the Gq trimeric GTPase? A. Elevation of intracellular cGMP levels, leading to the activation of protein kinase G B. Elevation of IP3 in the plasma membrane, leading to the activation of protein kinase D C. Elevation of intracellular Ca2+ levels, leading to the activation of protein kinase C D. Elevation of intracellular cAMP levels, leading to the activation of protein kinase A E. 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

What is the correct order of stages of the cell cycle, ordered longest to shortest, in mammalian cells in culture? A. G1 > G2 > S > M B. G1 > S = G2 > M C. G1 > S > G2 > M D. S > G1 > G2 > M E. S > G1 = G2 > M

C. G1 > S > G2 > M

Which protein in the TNF-alpha signaling pathway serves a similar function to Hsp90 in the steroid hormone signaling pathway? A. p50 B. I-kB kinase C. I-kB alpha D. p65 E. E3 ligase

C. I-kB alpha

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. Which of the following best describes this form of intercellular signaling? A. Synaptic signaling B. Endocrine signaling C. Paracrine signaling D. Contact-dependent signaling

C. Paracrine signaling

Which of the following is a feature of the androgen receptor (AR)? A. The AR can bind to testosterone and transport it across the plasma membrane. B. The AR acts as a transcriptional repressor in the absence of testosterone. C. The AR's subcellular location can be controlled by masking and unmasking of amino acid motifs. D. Binding of testosterone to the AR induces it to bind Hsp90. E. Mutation of the AR's activation domain prevents it from binding to DNA.

C. The AR's subcellular location can be controlled by masking and unmasking of amino acid motifs.

Which of the following describes a negative feedback effect mediated by a scaffolding protein? A. The activity of phospholipase Cb on PKC. B. The activity of Ras on MAP3K. C. The activity of PKA on a cAMP PDE. D. The activity of STATs on SOCS proteins

C. The activity of PKA on a cAMP PDE.

What would happen to the cell cycle in S. pombe yeast cells in liquid culture that have a temperature sensitive mutation that inactivates separase one hour after the culture is incubated at the restrictive temperature? A. The cells would still be in different phases of the cell cycle. B. The cells would all be arrested in G0. C. The cells would all be arrested in M-phase. D. The cells would all be dead. E. The cells would still be in different stages of the cell cycle but would have abnormal numbers of chromosomes

C. The cells would all be arrested in M-phase.

Which of the following can act as a GAP for a heterotrimeric GTPase? A. A GPCR B. GDP C. The target of the alpha subunit of the GTPase D. The beta-gamma subunits of the GTPase E. A GRK

C. The target of the alpha subunit of the GTPase

Evolutionary biology studies have identified the most invariant (conserved) amino acids found within the SH2 domain family. Which of the following is true regarding these invariant amino acids? A. The invariant amino acids generally have negatively charged side chains. B. The amino acids at these sites are generally hydrophobic. C. These amino acids have an important function in allowing binding of the SH2 domain to a phosphorylated tyrosine. D. These sites evolve (change) relatively quickly because they have critical functions. E. Mutation in these sites generally keeps the protein functional.

C. These amino acids have an important function in allowing binding of the SH2 domain to a phosphorylated tyrosine.

Which of the following statements about monomeric GTPases is false? A. They can bind either GDP or GTP B. They have enzymatic activity C. They phosphorylate a protein D. They act as binary (on-off) switches

C. They phosphorylate a protein

Select the correct phrase to complete the following sentence. "All nuclear hormone receptors ..." A. are cytosolic proteins that enter the nucleus upon ligand binding. B. are transcriptional repressors in the absence of their ligand. C. have ligand-binding and DNA-binding domains, and can directly bind to DNA. D. bind to steroid hormones. E. are transcriptional activators when bound to their ligand.

C.have ligand-binding and DNA-binding domains, and can directly bind to DNA.

Which of the following features would be unlikely to be found in an effective signaling molecule? A. Ability to be synthesized rapidly. B. Ability to be degraded rapidly. C. Ability to be stored, released and recovered. D. Ability to bind to all transmembrane receptors. E. Ability to be transported from the site of synthesis to a site of action.

D. Ability to bind to all transmembrane receptors.

Which of the following might be expected to directly turn off calmodulin activity? A. Opening a plasma membrane voltage gated sodium ion channel. B. Turning off a plasma membrane potassium ion channel. C. A rapid increase in the concentration of GTP in the cytoplasm. D. Activating a plasma membrane calcium ion pump. E. Release of GDP from the activated calmodulin.

D. Activating a plasma membrane calcium ion pump.

Which of the following describes a correct order of events that occurs during signaling between to induce vasodilation? A. Endothelial cell secretes acetylcholine -> G-protein coupled receptor in smooth muscle cell binds to guanylyl cyclase -> [increased cGMP] induces protein kinase G activity that leads to smooth muscle relaxation. B. Acetylcholine bind to G-protein coupled receptor on surface of smooth muscle cell ->smooth muscle cell synthesizes nitric oxide (NO) -> NO diffuses into endothelial cell ->activates guanylyl cyclase -> [increased cGMP] leads to smooth muscle relaxation. C. Activation of Ca2+- calmodulin in endothelial cell -> smooth muscle cell synthesizes nitric oxide (NO) -> NO activates guanylyl cyclase -> [increased cGMP] leads to smooth muscle relaxation. D. Activation of nitric oxide synthase in endothelial cell -> NO activates guanylyl cyclase in smooth muscle cell -> [increased cGMP] leads to smooth muscle relaxation.

D. Activation of nitric oxide synthase in endothelial cell -> NO activates guanylyl cyclase in smooth muscle cell -> [increased cGMP] leads to smooth muscle relaxation.

Molecule "Y" is a second messenger, whose lifespan in cells is 10 min. Following stimulation of a cell surface receptor, production of Y increases one hundred-fold. An increase in concentration of Y is required to mediate a decrease in the activity of enzyme "Z". What best describes the effect on this signaling pathway if the lifespan of Y was changed to 10 sec? A. Activity of Z will increase more rapidly. B. Activity of Z will decrease more slowly. C. Activity of Z will increase more slowly. D. Activity of Z will decrease more rapidly

D. Activity of Z will decrease more rapidly

Which of the following is NOT considered to be a common second messenger in cell signaling? A. Diacylglycerol B. Inositol triphosphate C. Cyclic adenosine monophosphate D. Adenosine triphosphate E. Ca2+

D. Adenosine triphosphate

Which domain in a steroid hormone receptor is not required for it to become active in the nucleus? A. The DNA binding domain. B. The transcriptional co-activator domain. C. The ligand binding domain. D. All of the above domains are required for a steroid hormone receptor to be active.

D. All of the above domains are required for a steroid hormone receptor to be active.

Which of the following directly helps PKC phosphorylate cytosolic proteins located close to the plasma membrane? A. IP4 B. Orai channels C. PIP2 D. DAG E. GPCR

D. DAG

Which of the following signals doesn't need a plasma membrane receptor to enter a cell? A. Insulin - a hormone. B. Adenosine - a purine nucleoside. C. HIV - a virus. D. Estrogen - a steroid hormone. E. Ferrous iron - Fe2+

D. Estrogen - a steroid hormone.

Which of the following properties would be found in a ligand that does not require a transmembrane receptor? A. It is hydrophilic. B. It can bind directly to DNA. C. It is always present at a higher concentration outside thecell relative to the cytoplasm. D. It is hydrophobic. E. It is a zwitterion.

D. It is hydrophobic.

Which molecular motors are inactive and which are active during anaphase B of mitosis? A. Myosin II is active, inter-polar (-) end kinesin motors are active, inter-polar (+) end kinesin motors are inactive and astral microtubule dynein motors are active. B. Myosin II is inactive, inter-polar (-) end kinesin motors are active, inter-polar (+) end kinesin motors are inactive and astral microtubule dynein motors are active. C. Myosin II is active, inter-polar (-) end kinesin motors are inactive, inter-polar (+) end kinesin motors are inactive and astral microtubule dynein motors are active. D. Myosin II is inactive, inter-polar (-) end kinesin motors are inactive, inter-polar (+) end kinesin motors are active and astral microtubule dynein motors are active. E. Myosin II is active, inter-polar (-) end kinesin motors are active, inter-polar (+) end kinesin motors are active and astral microtubule dynein motors are active.

D. Myosin II is inactive, inter-polar (-) end kinesin motors are inactive, inter-polar (+) end kinesin motors are active and astral microtubule dynein motors are active.

Which of the following "feedback" systems would be suited to allow a cell to respond to long-term but not short-term signals? A. A positive feedback loop. B. A negative feedback loop. C. A feed-forward loop. D. None of the above feedback systems is suited to allow a cell to respond to a long-term but not short-term signal

D. None of the above feedback systems is suited to allow a cell to respond to a long-term but not short-term signal

You are given a novel drug that inhibits the activity of a GPCR kinase (GRK) specific for GPCR's that bind adrenaline (epinephrine). You know that adrenaline increases heart rate and activates adenylyl cyclase leading to breakdown of glycogen in muscle. You inject two rats. Rat #1 is given an injection of the novel drug followed by adrenaline, while rat #2 is injected with adrenaline only. Which of the following would you find when you analyze the rats 5 min after injection of adrenaline? A. Rat # 1 has increased glycogen and increased cAMP in muscle, and increased heart rate relative to Rat #2 B. Rat # 1 has decreased glycogen and decreased cAMP in muscle, and decreased heart rate relative to Rat #2 C. Rat # 1 has decreased glycogen and increased cAMP in muscle, and decreased heart rate relative to Rat #2 D. Rat # 1 has decreased glycogen and increased cAMP in muscle, and increased heart rate relative to Rat #2 E. No difference in levels of glycogen and cAMP in muscle, and heart rate in rat #1 compared to rat #2

D. Rat # 1 has decreased glycogen and increased cAMP in muscle, and increased heart rate relative to Rat #2

Which of the following is not a general principle of signaling in multi-cellular eukaryotes? A. Many signals can be amplified or dampened by the cell. B. Some cells respond to the same signal in different ways. C. A signal can activate more than one signaling pathway in a cell. D. Signaling pathways seldom share components with other pathways. E. Cells are constantly bombarded by signals.

D. Signaling pathways seldom share components with other pathways.

Which of the following describes an example of positive feedback that occurs during the cell cycle? A. None of the above is an example of an event involving positive feedback. B. Phosphorylation of Rb by G1-Cyclin/CDK C. Activation of a CDK by a cyclin. D. Stimulation of transcription of E2F gene by E2F protein. E. Phosphorylation of Sic1 by G1/S Cyclin/CDK.

D. Stimulation of transcription of E2F gene by E2F protein.

Which of the following best describes how an I-Smad (e.g. Smad7) participates in regulation of signaling via TGF-b family member receptors? A. The I-Smad co-associates with R-Smads and Co-Smads (e.g. Smad 4) and prevents activation of gene expression in the nucleus by interfering with binding to DNA. B. The I-Smad binds with R-Smads only and prevents R-Smads from activating gene expression in the nucleus. C. The I-Smad binds the the Type-I receptor and once phosphorylated interacts with and prevents R-Smads from being imported to the nucleus to mediate gene expression. D. The I-Smad binds to the Type-I receptor but cannot be phosphorylated by it, thereby preventing interaction of R-Smads with the receptor

D. The I-Smad binds to the Type-I receptor but cannot be phosphorylated by it, thereby preventing interaction of R-Smads with the receptor

What is the most likely effect of greatly increasing the activity of cAMP phosphodiesterase (cAMP PDE) throughout the cell? A. G alpha cannot be activated. B. Signaling via the G beta/gamma is blocked. C. PKG cannot be activated. D. The catalytic subunits of PKA cannot dissociate from the regulatory subunit. E. cAMP-mediated signaling is not affected.

D. The catalytic subunits of PKA cannot dissociate from the regulatory subunit.

Which statement best describes how molecular complementarity enables specificity during a signaling event? A. The molecular shape of two molecules should have a large amount of overall complementarity that involves covalent interactions at multiple different sites. B. The molecular shape of two molecules should have a small amount of complementarity. C. The molecular shape of two molecules should have a large amount of overall complementarity that involves strong interactions at multiple different sites. D. The molecular shape of two molecules should have a large amount of overall complementarity that involves weak interactions at multiple different sites.

D. The molecular shape of two molecules should have a large amount of overall complementarity that involves weak interactions at multiple different sites.

Which of the following statements about CKI proteins is false? A. They are degraded via poly-ubiquitination. B. They are synthesized during each cell cycle. C. They are essential for the function of several checkpoints. D. They activate mitotic CDK

D. They activate mitotic CDK

Cholera toxin ADP-ribosylates the α subunit of stimulatory G protein (Gs), thereby blocking GTP hydrolysis. By contrast, pertussis toxin ADP-ribosylates the α subunit of inhibitory G protein (Gi) and prevents its interaction with the GPCR. 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 decrease cAMP concentration. D. They both tend to increase cAMP concentration.

D. They both tend to increase cAMP concentration.

Which of the following statements about heterotrimeric GTPases is false? A. They can bind either GDP or GTP B. The participate in signal amplification C. They have enzymatic activity D. They phosphorylate a target protein E. They act as binary (on-off) switches

D. They phosphorylate a target protein

Which of the following best explains how the NLS of a STAT protein normally becomes exposed during a signaling event? A. Through mono-ubiquitination by a SOCS protein. B. Through phosphorylation of the STAT by a serine kinase, causing it to associate with a receptor. C. Through dephosphorylation of the STAT by a phosphatase, causing a conformational change that exposes the NLS. D. Through phosphorylation of the STAT causing it to dimerize. E. Through binding of the STAT to a JAK, causing a conformational change that exposes the STAT's NLS.

D. Through phosphorylation of the STAT causing it to dimerize.

What event immediately precedes activation of S-phase cyclin-CDK? A. A kinase that activates an inhibitor of S-cyclins. B. A phosphatase that activates an activator of S-cyclins. C. A kinase that activates an activator of S-cyclins. D. Ubiquitination and degradation of an inhibitor of S-cyclins. E. A phosphatase that inhibits an inhibitor of S-cyclins.

D. Ubiquitination and degradation of an inhibitor of S-cyclins.

Which of the following is NOT a common mechanism used to regulate activity of signaling proteins? A. Binding of another molecule to the signaling protein B. Masking of a NLS signal in the signaling protein by another protein C. Degradation of the signaling molecule by proteolysis D. Uptake of the signaling protein by the ER E. Covalent modification of a protein involved in a signaling pathway (e.g. phosphorylation)

D. Uptake of the signaling protein by the ER

Sort the following events to reflect the normal order in which they occur in G-protein-coupled receptor signaling leading to transcription of genes that have a cAMP response element. (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

DBCA

Which of the following is not a commonly used mechanism to regulate activity of proteins in a signaling pathway? A. Phosphorylation. B. Unmasking of a nuclear localization signal (NLS). C. Proteolytic degradation. D. Protein synthesis. E. All of the above are examples of commonly used mechanisms to regulate proteins in a signaling pathway.

E. All of the above are examples of commonly used mechanisms to regulate proteins in a signaling pathway.

Which of the following events can restore the sensitivity of a de-sensitized GPCR? A. Endocytosis of the GPCR B. Continuous stimulation of the GPCR C. Binding of a GRK to a GPCR D. Binding of ATP to the cytosolic region of the GPCR E. De-phosphorylation of the GPCR

E. De-phosphorylation of the GPCR

Which stages of the cell cycle are absent from cells during early embryonic development of Xenopus frog embryos? A. G1 and S B. G1 and M C. G2 and S D. S and M E. G0 and G2

E. G0 and G2

Which of the following molecules could best be categorized as functioning by "Transducing and Amplifying" a signal? A. Citrulline in NO signaling B. E3 ligase in TNF-alpha signaling C. Retinoic Acid Receptor (RAR) without ligand in nuclear hormone receptor signaling. D. Hsp90 in androgen receptor signaling E. Guanylyl cyclase in NO signaling

E. Guanylyl cyclase in NO signaling

Which of the following changes in gene expression could overcome an abnormal cell cycle in fission yeast resulting from excess CDC25 activity? A. Decrease Wee1 activity. B. Increase CAK activity. C. Decrease Wee1 activity and increase CAK activity. D. Increase expression of M-cyclin. E. Increase Wee1 activity.

E. Increase Wee1 activity.

Which of the following proteins is the product of an immediate early gene expressed following mitogenic stimulation of cell-cycle entry? A. G1-cyclins B. All of the above C. Rb D. E2F E. Myc

E. Myc

Which statement about cell surface receptors with intrinsic or associated enzyme activity is false? A. Some receptors dimerize before binding ligand B. The genes for some receptors encode kinase activity, while others do not C. Receptors commonly recruit signaling proteins via phosphorylation of the receptor's cytoplasmic region. D. Receptors always undergo a conformational change upon binding of ligand E. None of the above statements is false

E. None of the above statements is false

Which of the following statements is false? A. Binding of GTP to a GTPase causes a conformational change in the GTPase. B. Unbinding of Ca2+ to calmodulin produces a change in the conformation of calmodulin. C. Phosphorylation of a MAPK produces a conformational change in the kinase's lip domain. D. Hydrolysis of GTP by a GTPase can be influenced by interaction of the GTPase and its target protein. E. None of the statements is false

E. None of the statements is false

Which of the following statements about the estrogen receptor (ER) and the retinoic acid receptor (RAR) is true? A. The ER has a nuclear localization signal (nls) while the RAR does not. B. The ER and RAR can each act as a transcriptional repressor while located in the nucleus. C. The ER and RAR can bind the same ligands. D. The RAR can signal while located at the inner leaflet of the plasma membrane. E. The RAR and the ER each have a DNA binding domain.

E. The RAR and the ER each have a DNA binding domain.

Which of the following statements about M-cyclin proteins is false? A. They are degraded via poly-ubiquitination. B. They are synthesized during each cell cycle. C. They are present in the cell during G2. D. They activate mitotic CDK. E. Their presence is required for the cell to exit mitosis

E. Their presence is required for the cell to exit mitosis

Which of the following statements about M-cyclin proteins is false? A. They are degraded via poly-ubiquitination. B. They are synthesized during each cell cycle. C. They are present in the cell during G2. D. They activate mitotic CDK. E. Their presence is required for the cell to exit mitosis.

E. Their presence is required for the cell to exit mitosis.

What caused premature condensation of G1-phase chromosomes in a cell fused with a cell in mitosis? A. Something in the nucleus of the cell in mitosis. B. Something in the cytoplasm of the cell in mitosis. C. The condensed mitotic chromosomes signaled to the non-condensed chromosomes to undergo condensation. D. Something attached to the plasma membrane of the mitotic cell. E. Without additional experiments, it is impossible to tell what caused premature condensation of the G1 chromosomes and where the activity is localized in the cell.

E. Without additional experiments, it is impossible to tell what caused premature condensation of the G1 chromosomes and where the activity is localized in the cell.

A kinase modifies the side chain of two serine and three threonine amino acids in a protein. Which of the following statements are true or false regarding the non-phosphorylated protein and the phosphorylated protein? 1. The phosphorylated protein has a smaller molecular mass than the non-phosphorylated protein. 2. The overall (net) charge of the non-phosphorylated protein is more positive compared to the phosphorylated protein. 3. The phosphorylated protein might be more likely to interact with proteins containing a SH2 and a PTB domain. 4. The non-phosphorylated protein might be more likely to interact with proteins containing a SH2 and a PTB domain.

FTFF

Which of the following statements describes a method by which signaling via TGF-beta and BMP receptors is decreased? (Select all that apply) I SMAD-mediated expression of a protein that acts in the nucleus to block SMAD-dependent signaling. II SMAD-mediated expression of a SMAD that cannot be phosphorylated by a TGF-beta/BMP receptor complex. III SMAD-mediated histone acetylation of genes whose expression are regulated by SMADs. IV SMAD-dependent phosphorylation of the cytoplasmic receptor tails of type-I TGF-beta/BMP receptors.

I and II

In addition to control of cell growth and division, Mitogen-Activated Protein Kinases (MAPKs) have important functions in several other important cellular processes including differentiation, survival and apoptosis. Consequently, to minimize the risk of developmental defects and cancer, the control of MAPK activation must be carefully regulated. Which of the following helps to minimize inappropriate MAPK activity? I MAPKs are only activated by MAP2Ks. II MAPKs can only be activated after release of ADP. III MAPKs must be phosphorylated on both threonine and tyrosine to become fully active.

I and III

Which of the following statements concerning STAT proteins is / are true? I STATs can interact with proteins via a phospho-tyrosine on the interacting protein. II STATs can interact with proteins via a phospho-serine on the interacting protein. III STATs can bind to a phosphorylated JAK. IV STATs can form homo-dimers.

I and IV

Which of the following receptor signaling pathways use phosphorylation to cause exposure of a NLS so that a signaling protein can be targeted to the nucleus? I TNF-alpha signaling II RTK Signaling III TGF-beta signaling IV Cytokine signaling

I, III, and IV

In some signaling pathways, phosphorylation of amino acids in the cytoplasmic domain of the cell surface transmembrane receptor increases the affinity between the cytoplasmic domain of the receptor and non-transmembrane cytoplasmic proteins. In turn, interaction of the non-transmembrane cytoplasmic proteins with the cytoplasmic tail of the receptor causes the non-transmembrane proteins to become phosphorylated, which allows the non-transmembrane proteins to directly regulate transcription. Which domains and motifs might you find in the "non-transmembrane proteins" described in the above statement ? I SH2 domain II SH3 domain III GTP binding domain IV MH2 domain V NLS motif

I, IV, and V

Ras GTPase was first discovered as being a gene that can change normal cells into cancer cells. Ras is normally activated by a receptor tyrosine kinase (RTK). However, in many cancers the Ras gene is mutated in a way that makes its signaling hyperactive. The hyperactive Ras conveys signals that drive cell division and tumor growth. You have learned that activated Ras can bind MAP3K, which in turn activates MAP2K, which activates MAPK that targets effector molecules leading to cell growth and division.What types of mutations in a Ras gene could produce hyperactive signaling Ras? I - Missense mutations that stimulate Ras to bind Ras GTPase-activating proteins. II - Missense mutations that decrease the ability of Ras to hydrolyze GTP. III - Missense mutations that prevent Ras from binding to Ras-GEF

II - Missense mutations that decrease the ability of Ras to hydrolyze GTP.

Signaling via cytokine receptors can occur via STATs and this signaling can be negatively regulated by SHP1. Assume that the SH2 domain in a STAT and the SH2 domain in SHP1 interact with the same phosphorylated amino acid in the C-terminal tail of a cytokine receptor. Also assume that when SHP1 is expressed, there is only one molecule of SHP1 for every 10 molecules of STAT. Despite this, SHP1 is extremely efficient at inactivating STAT-dependent signaling via the cytokine receptor. Which of the following statements would you predict to be true ? I The STAT's SH2 domain has higher affinity for the phosphorylated amino acid compared to SHP1's SH2 domain. II The STAT's SH2 domain has lower affinity for the phosphorylated amino acid compared to SHP1's SH2 domain. III The STAT's SH2 domain has the same affinity for the phosphorylated amino acid compared to SHP1's SH2 domain. IV SHP1 protein is likely to be expressed in cells immediately before the cytokine receptor is activated. V SHP1 protein is likely to be expressed in cells after the cytokine receptor is activated.

II and V

Which of the following events is an example of negative feedback in a signaling pathway ? I Binding of the beta/gamma subunits to an alpha subunit of a heterotrimeric GTPase. II Binding of an I-Smad to a TGF-beta type-I receptor. III Binding of a GEF to a monomeric GTPase. IV Binding of a GAP to a monomeric GTPase. V Calcium-calmodulin mediated activation of a membrane localized Ca2+ pump that moves Ca2+ out of the cytoplasm.

II, IV, and V

In a key experiment that lead to the discovery of cyclins, culture media lacking the essential amino acid methionine was supplemented with radioactive S35-methionine before adding clam eggs that were fertilized immediately afterwards with sperm. At regular intervals during the first few cell divisions of the resulting clam embryos, some of the embryos were removed from the dish, and their proteins were extracted and analyzed by protein gel electrophoresis followed by radiography using X-ray film. What was / were the key conclusion(s) from this experiment that allowed the researchers to postulate the existence of cyclins ? I Some proteins were synthesized before fertilization of eggs. II The concentration of some newly synthesized proteins increased steadily and continuously after fertilization. III The concentration of some newly synthesized proteins increased as the cells of the embryos transitioned from interphase to mitosis. IV Some radioactively labeled proteins were not present in each sample from the time-course experiment.

III and IV

In a key experiment that lead to the discovery of cyclins, culture media lacking the essential amino acid methionine was supplemented with radioactive S35-methionine before adding clam eggs that were fertilized immediately afterwards with sperm. At regular intervals during the first few cell divisions of the resulting clam embryos, some of the embryos were removed from the dish, and their proteins were extracted and analyzed by protein gel electrophoresis followed by radiography using X-ray film. Why was S35-methionine added to the media in which the eggs were fertilized ? I To label all proteins present in the eggs at the time they were isolated from the clams. II To label all proteins present in the sperm at the time they were isolated from the clams. III To label all proteins present in the clam embryos at the time of fertilization. IV To label proteins that were synthesized in the clam embryos starting after fertilization.

IV

Indicate true (T) or false (F) for the statements below regarding cellular signaling mediated by nitric oxide (NO). Your final answer will be a four-letter string composed of letters T and F only, e.g. TTTF. ( ) Once produced, NO can diffuse to neighboring cells. ( ) The lifetime of NO is 5 - 10 minutes. ( ) NO normally decreases cGMP concentration by directly activating cGMP phosphodiesterase. ( ) The drug Viagra® counteracts the effects of NO on penile blood vessels.

TFFF