Deck 16: Cell Signaling

Question 1

During the mating process, yeast cells respond to pheromones secreted by other yeast cells.These pheromones bind GPCRs on the surface of the responding cell and lead to the activation of G proteins inside the cell.When a wild-type yeast cell senses the pheromone, its physiology changes in preparation for mating: the cell stops growing until it finds a mating partner.If yeast cells do not undergo the appropriate response after sensing a pheromone, they are considered sterile.Yeast cells that are defective in one or more components of the G protein have characteristic phenotypes in the absence and presence of the pheromone, which are listed in Table 16-14. $$\begin{array} { l l l } & {\underline{ \quad\quad\quad\quad\quad\quad\text { phenotype\quad\quad\quad\quad }} } \\ \text { mutation } & \text { minus pheromone } & \text { plus pheromone } \\\hline \text { none (wild type) } & \text { normal growth } & \text { arrested growth, mating response } \\\alpha \text { subunit deleted } & \text { arrested growth } & \text { arrested growth, sterile } \\\beta \text { subunit deleted } & \text { normal growth } & \text { normal growth, sterile } \\\gamma \text { subunit deleted } & \text { normal growth } & \text { normal growth, sterile } \\\alpha \text { and } \beta \text { deleted } & \text { normal growth } & \text { normal growth, sterile } \\\alpha \text { and } \gamma \text { deleted } & \text { normal growth } & \text { normal growth, sterile } \\\beta \text { and } \gamma \text { deleted } & \text { normal growth } & \text { normal growth, sterile }\end{array}$$ Table 16-14
Which of the following models is consistent with the data from the analysis of these mutants? Explain your answer.

A)The ? subunit activates the mating response but is inhibited when bound to ??.
B)The ?? subunit activates the mating response but is inhibited when bound to ?.
C)The G protein is inactive; either the free ? or free ?? complex is capable of activating the mating response.
D)The G protein is active; both free ? and free ?? complex are required to inhibit the mating response.

Answer 1

The ?? subunit activates the mating response but is inhibited when bound to ?.

Question 2

Which of the following statements about G-protein-coupled receptors (GPCRs) is FALSE?

A)GPCRs are the largest family of cell-surface receptors in humans.
B)GPCRs are used in endocrine, paracrine, and neuronal signaling.
C)GPCRs are found in yeast, mice, and humans.
D)The different classes of GPCR ligands (proteins, amino acid derivatives, or fatty acids) bind to receptors with different numbers of transmembrane domains.

Answer 2

D

Question 3

Acetylcholine binds to a GPCR on heart muscle, making the heart beat more slowly.The activated receptor stimulates a G protein, which opens a K⁺ channel in the plasma membrane, as shown in Figure 16-13.Which of the following would enhance this effect of the acetylcholine? Figure 16-13

A)addition of a high concentration of a nonhydrolyzable analog of GTP
B)addition of a drug that prevents the α subunit from exchanging GDP for GTP
C)mutations in the acetylcholine receptor that weaken the interaction between the receptor and acetylcholine
D)mutations in the acetylcholine receptor that weaken the interaction between the receptor and the G protein

Answer 3

A
A constitutively active phospholipase C will lead to the constitutive production of IP₃ and diacylglycerol, leading to activation of PKC in a signal-independent manner; thus, Rafty activation and the lipid modification will be signal-independent.A mutation in the GPCR that bind the signal more tightly and a Ca²⁺ channel with an increased affinity for IP will increase activity of the signal transduction pathway in a signal-dependent manner.A mutation that renders Rafty such that it can no longer by phosphorylated by PKC will prevent PKC from activating Rafty and will thus prevent the lipid modifications.

Question 4

Foreign substances like nicotine, morphine, and menthol exert their initial effects by

A)killing cells immediately, exerting their physiological effects by causing cell death.
B)diffusing through cell plasma membranes and binding to transcription factors to change gene expression.
C)interacting with cell-surface receptors, causing the receptors to transduce signal inappropriately in the absence of the normal stimulus.
D)removing cell-surface receptors from the plasma membrane.

Question 5

Activated protein kinase C (PKC) can lead to the modification of the membrane lipids in the vicinity of the active PKC.Figure 16-17 shows how G proteins can indirectly activate PKC.You have discovered the enzyme activated by PKC that mediates the lipid modification.You call the enzyme Rafty and demonstrate that activated PKC directly phosphorylates Rafty, activating it to modify the plasma membrane lipids in the vicinity of the cell where PKC is active; these lipid modifications can be detected by dyes that bind to the modified lipids.Cells lacking Rafty do not have these modifications, even when PKC is active.Which of the following conditions would lead to signal-independent modification of the membrane lipids by Rafty? Figure 16-17

A)the expression of a constitutively active phospholipase C
B)a mutation in the GPCR that binds the signal more tightly
C)a Ca²⁺ channel in the endoplasmic reticulum with an increased affinity for IP₃
D)a mutation in the gene that encodes Rafty such that the enzyme can no longer be phosphorylated by PKC

Question 6

The lab you work in has discovered a previously unidentified extracellular signal molecule called QGF, a 75,000 -dalton protein.You add purified QGF to different types of cells to determine its effect on these cells.When you add QGF to heart muscle cells, you observe an increase in cell contraction.When you add it to fibroblasts, they undergo cell division.When you add it to nerve cells, they die.When you add it to glial cells, you do not see any effect on cell division or survival.Given these observations, which of the following statements is most likely to be TRUE?

A)Because it acts on so many diverse cell types, QGF probably diffuses across the plasma membrane into the cytoplasm of these cells.
B)Glial cells do not have a receptor for QGF.
C)QGF activates different intracellular signaling pathways in heart muscle cells, fibroblasts, and nerve cells to produce the different responses observed.
D)Heart muscle cells, fibroblasts, and nerve cells must all have the same receptor for QGF.

Question 7

You are interested in how cyclic-AMP-dependent protein kinase A (PKA) functions to affect learning and memory, and you decide to study its function in the brain.It is known that, in the cells you are studying, PKA works via a signal transduction pathway like the one depicted in Figure 16-15.Furthermore, it is also known that activated PKA phosphorylates the transcriptional regulator called Nerd that then activates transcription of the gene Brainy.Which situation described below will lead to an increase in Brainy transcription? Figure 16-15

A)a mutation in the Nerd gene that produces a protein that cannot be phosphorylated by PKA
B)a mutation in the nuclear import sequence of PKA from PPKKKRKV to PPAAAAAV
C)a mutation in the gene that encodes cAMP phosphodiesterase that makes the enzyme inactive
D)a mutation in the gene that encodes adenylyl cyclase that renders the enzyme unable to interact with the α subunit of the G protein

Question 8

Which of the following statements about molecular switches is FALSE?

A)Phosphatases remove the phosphate from GTP on GTP-binding proteins, turning them off.
B)Protein kinases transfer the terminal phosphate from ATP onto a protein.
C)Serine/threonine kinases are the most common types of protein kinase.
D)A GTP-binding protein exchanges its bound GDP for GTP to become activated.

Question 9

Which of the following statements is TRUE?

A)Extracellular signal molecules that are hydrophilic must bind to a cell-surface receptor so as to signal a target cell to change its behavior.
B)To function, all extracellular signal molecules must be transported by their receptor across the plasma membrane into the cytosol.
C)A cell-surface receptor capable of binding only one type of signal molecule can mediate only one kind of cell response.
D)Any foreign substance that binds to a receptor for a normal signal molecule will always induce the same response that is produced by that signal molecule on the same cell type.

Question 10

Adrenaline stimulates glycogen breakdown in skeletal muscle cells by ultimately activating glycogen phosphorylase, the enzyme that breaks down glycogen, as depicted in Figure 16-16. Figure 16-16
Which of the following statements is FALSE?

A)A constitutively active mutant form of PKA in skeletal muscle cells would lead to a decrease in the amount of unphosphorylated phosphorylase kinase.
B)A constitutively active mutant form of PKA in skeletal muscle cells would not increase the affinity of adrenaline for the adrenergic receptor.
C)A constitutively active mutant form of PKA in skeletal muscle cells would lead to an excess in the amount of glucose available.
D)A constitutively active mutant form of PKA in skeletal muscle cells would lead to an excess in the amount of glycogen available.

Question 11

Which of the following statements is TRUE?

A)Because endocrine signals are broadcast throughout the body, all cells will respond to the hormonal signal.
B)The regulation of inflammatory responses at the site of an infection is an example of paracrine signaling.
C)Paracrine signaling involves the secretion of signals into the bloodstream for distribution throughout the organism.
D)The axons of neurons typically signal target cells using membrane-bound signaling molecules that act on receptors in the target cells.

Question 12

Acetylcholine is a signaling molecule that elicits responses from heart muscle cells, salivary gland cells, and skeletal muscle cells.Which of the following statements is FALSE?

A)Heart muscle cells decrease their rate and force of contraction when they receive acetylcholine, whereas skeletal muscle cells contract.
B)Heart muscle cells, salivary gland cells, and skeletal muscle cells all express an acetylcholine receptor that belongs to the transmitter-gated ion channel family.
C)Active acetylcholine receptors on salivary gland cells and heart muscle cells activate different intracellular signaling pathways.
D)Heart muscle cells, salivary gland cells, and skeletal muscle cells all respond to acetylcholine within minutes of receiving the signal.

Question 13

You are interested in cell-size regulation and discover that signaling through a GPCR called ERC1 is important in controlling cell size in embryonic rat cells.The G protein downstream of ERC1 activates adenylyl cyclase, which ultimately leads to the activation of PKA.You discover that cells that lack ERC1 are 15% smaller than normal cells, while cells that express a mutant, constitutively activated version of PKA are 15% larger than normal cells.Given these results, which of the following treatments to embryonic rat cells should lead to smaller cells?

A)addition of a drug that causes cyclic AMP phosphodiesterase to be hyperactive
B)addition of a drug that prevents GTP hydrolysis by Gα
C)addition of a drug that activates adenylyl cyclase
D)addition of a drug that mimics the ligand of ERC1

Question 14

During nervous-system development in Drosophila, the membrane-bound protein Delta acts as an inhibitory signal to prevent neighboring cells from developing into neuronal cells.Delta is involved in __________ signaling.

A)endocrine
B)paracrine
C)neuronal
D)contact-dependent

Question 15

The following happens when a G-protein-coupled receptor activates a G protein.

A)The β subunit exchanges its bound GDP for GTP.
B)The GDP bound to the α subunit is phosphorylated to form bound GTP.
C)The α subunit exchanges its bound GDP for GTP.
D)It activates the α subunit and inactivates the βγ complex.

Question 16

The length of time a G protein will signal is determined by the

A)activity of phosphatases that turn off G proteins by dephosphorylating Gα.
B)activity of phosphatases that turn GTP into GDP.
C)degradation of the G protein after Gα separates from Gβγ.
D)GTPase activity of Gα.

Question 17

Figure 16-20 shows the pathway through which nitric oxide (NO) triggers smooth muscle relaxation in a blood vessel wall.Which of the following situations would lead to relaxation of the smooth muscle cells in the absence of acetylcholine? Figure 16-20

A)a smooth muscle cell that has a defect in guanylyl cyclase such that it cannot bind NO
B)a muscle cell that has a defect in guanylyl cyclase such that it constitutively converts GTP to cyclic GMP
C)a muscle cell that has cyclic GMP phosphodiesterase constitutively active
D)a drug that blocks an enzyme involved in the metabolic pathway from arginine to NO

Question 18

When a signal needs to be sent to most cells throughout a multicellular organism, the signal most suited for this is a

A)neurotransmitter.
B)hormone.
C)dissolved gas.
D)scaffold.

Question 19

The local mediator nitric oxide stimulates the intracellular enzyme guanylyl cyclase by

A)activating a G protein.
B)activating a receptor tyrosine kinase.
C)diffusing into cells and stimulating the cyclase directly.
D)activating an intracellular protein kinase.

Question 20

Cell lines A and B both survive in tissue culture containing serum but do not proliferate.Factor F is known to stimulate proliferation in cell line A.Cell line A produces a receptor protein (R) that cell line B does not produce.To test the role of receptor R, you introduce this receptor protein into cell line B, using recombinant DNA techniques.You then test all of your various cell lines in the presence of serum for their response to factor F, with the results summarized in Table 16-9. $\begin{array} { l l l } \text { Cell line } & \text { Factor } F & \text { Response } \\\hline \text { A } & \text { - Factor F } & \text { Cells do not proliferate } \\\text { A } & \text { + Factor F } & \text { Cells proliferate } \\\text { B } & \text { - Factor F } & \text { Cells do not proliferate } \\\text { B } & \text { + Factor F } & \text { Cells do not proliferate } \\\text { B + receptor R } & \text { - Factor } F & \text { Cells proliferate } \\\text { B + receptor R } & \text { + Factor F } & \text { Cells proliferate }\end{array}$ Table 16-9
Which of the following cannot be concluded from your results above?

A)Binding of factor F to its receptor is required for proliferation of cell line A.
B)Receptor R binds to factor F to induce cell proliferation in cell line A.
C)Cell line A expresses a receptor for factor F.
D)Factor F is not required for proliferation in cell line B.

Question 21

The ethylene response in plants involves a dimeric transmembrane receptor.When the receptor is not bound to ethylene, the receptor binds to and activates a protein kinase, which activates an intracellular signaling pathway that leads to the degradation of a transcriptional regulator important for transcribing the ethylene-responsive genes (see Figure 16-33).You discover a phosphatase that is important for ethylene signaling, and you name it PtpE.Plants lacking PtpE never turn on ethylene-responsive genes, even in the presence of ethylene.You find that PtpE dephosphorylates serine 121 on the transcriptional regulator.Furthermore, plants lacking PtpE degrade the transcriptional regulator in the presence of ethylene. (A) $\text { ABSENCE OF ETHYLENE }$


(B) $\text { PPESENCE OF ETHYLENE }$

Figure 16-33
Which of the following statements is inconsistent with your data?

A)When the transcriptional regulator is phosphorylated, it activates transcription of the ethylene-responsive genes.
B)When the transcriptional regulator is not phosphorylated, it binds to DNA.
C)Activation of the protein kinase that binds to the ethylene receptor leads to inactivation of PtpE.
D)Binding of ethylene to its receptor leads to the activation of PtpE.

Question 22

Which of the following statements is FALSE?

A)Nucleotides and amino acids can act as extracellular signal molecules.
B)Some signal molecules can bind directly to intracellular proteins that bind DNA and regulate gene transcription.
C)Some signal molecules are transmembrane proteins.
D)Dissolved gases such as nitric oxide (NO) can act as signal molecules, but because they cannot interact with proteins they must act by affecting membrane lipids.

Question 23

The growth factor Superchick stimulates the proliferation of cultured chicken cells.The receptor that binds Superchick is a receptor tyrosine kinase (RTK), and many chicken tumor cell lines have mutations in the gene that encodes this receptor.Which of the following types of mutation would be expected to promote uncontrolled cell proliferation?

A)a mutation that prevents dimerization of the receptor
B)a mutation that destroys the kinase activity of the receptor
C)a mutation that inactivates the protein tyrosine phosphatase that normally removes the phosphates from tyrosines on the activated receptor
D)a mutation that prevents the binding of the normal extracellular signal to the receptor

Question 24

Which of the following statements is TRUE?

A)MAP kinase is important for phosphorylating MAP kinase kinase.
B)PI 3-kinase phosphorylates a lipid in the plasma membrane.
C)Ras becomes activated when an RTK phosphorylates its bound GDP to create GTP.
D)Dimerization of GPCRs leads to Gα activation.

Question 25

A protein kinase can act as an integrating device in signaling if it

A)phosphorylates more than one substrate.
B)catalyzes its own phosphorylation.
C)is activated by two or more proteins in different signaling pathways.
D)initiates a phosphorylation cascade involving two or more protein kinases.

Question 26

For each of the following sentences, fill in the blanks with the best word or phrase selected from the list below.Not all words or phrases will be used; each word or phrase should be used only once.
amplification G protein phosphorylation
contact-dependent K⁺ channel receptor
endocrine neuronal target
epithelial paracrine
Cells can signal to each other in various ways.A signal that must be relayed to the entire body is most efficiently sent by __________ cells, which produce hormones that are carried throughout the body through the bloodstream.On the other hand, __________ methods of cell signaling do not require the release of a secreted molecule and are used for very localized signaling events.During __________ signaling, the signal remains in the neighborhood of the secreting cell and thus acts as a local mediator on nearby cells.Finally, __________ signaling involves the conversion of electrical impulses into a chemical signal.Cells receive signals through a __________, which can be an integral membrane protein or can reside inside the cell.

Question 27

Figure 16-34 shows that intracellular signaling pathways can be highly interconnected. Figure 16-34
From the information in Figure 16-34, which of the following statements is FALSE?

A)The GPCR and the RTK both activate phospholipase C.
B)Activation of either the GPCR or the RTK will lead to activation of transcriptional regulators.
C)CaM-kinase is only activated when the GPCR is active and not when the RTK is active.
D)Ras is activated only when the RTK is active and not when the GPCR is active.

Question 28

Explain why the signal molecules used in neuronal signaling work at a longer range than those used in contact-dependent signaling.

Question 29

Choose the phrase in each pair that is likely to occur more rapidly in response to an extracellular signal.
A.changes in cell secretion/increased cell division
B.changes in protein phosphorylation/changes in proteins being synthesized
C.changes in mRNA levels/changes in membrane potential

Question 30

Receipt of extracellular signals can change cell behavior quickly (for example, in seconds or less) or much more slowly (for example, in hours).
A.What kind of molecular changes could cause quick changes in cell behavior?
B.What kind of molecular changes could cause slow changes in cell behavior?
C.Explain why the response you named in A results in a quick change, whereas the response you named in B results in a slow change.

Question 31

List in order the following types of cell signaling from the type of signaling in which the signal molecule travels the least distance to the type of signaling in which the signal molecule travels the largest distance.
contact-dependent signaling neuronal signaling
endocrine signaling paracrine signaling

Question 32

Figure 16-36 shows how normal signaling works with a Ras protein acting downstream of an RTK.You examine a cell line with a constitutively active Ras protein that is always signaling.Which of the following conditions will turn off signaling in this cell line? Figure 16-36

A)addition of a drug that prevents protein X from activating Ras
B)addition of a drug that increases the affinity of protein Y and Ras
C)addition of a drug that blocks protein Y from interacting with its target
D)addition of a drug that increases the activity of protein Y

Question 33

All members of the nuclear receptor family

A)are cell-surface receptors.
B)do not undergo conformational changes.
C)are found only in the cytoplasm.
D)interact with signal molecules that diffuse through the plasma membrane.

Question 34

You are interested in further understanding the signal transduction pathway that controls the production of Pig1, a protein important for regulating cell size.Activation of the TRK receptor leads to activation of the GTP-binding protein, Ras, which then activates a protein kinase that phosphorylates the SZE transcription factor.SZE only interacts with the nuclear transport receptor when it is phosphorylated.SZE is a gene activator for the Pig1 gene.This pathway is diagrammed in Figure 16-25. Figure 16-25
Normal cells grown under standard conditions (without ligand) are 14 μm in diameter while normal cells exposed to TRK ligand are 10.5 μm in diameter.Given this situation, which of the following conditions do you predict will more likely lead to smaller cells?

A)addition of TRK ligand and a drug that stimulates the GTPase activity of Ras
B)addition of TRK ligand and a drug that inhibits the activity of the phosphatase that acts on SZE
C)addition of TRK ligand and a drug that stimulates the degradation of Pig1
D)addition of TRK ligand and a drug that inhibits Pig1 binding to DNA

Question 35

When Ras is activated, cells will divide.A dominant-negative form of Ras clings too tightly to GDP.You introduce a dominant-negative form of Ras into cells that also have a normal version of Ras.Which of the following statements is TRUE?

A)The cells you create will divide less frequently than normal cells in response to the extracellular signals that typically activate Ras.
B)The cells you create will run out of the GTP necessary to activate Ras.
C)The cells you create will divide more frequently compared to normal cells in response to the extracellular signals that typically activate Ras.
D)The normal Ras in the cells you create will not be able to bind GDP because the dominant-negative Ras binds to GDP too tightly.

Question 36

The activation of the serine/threonine protein kinase Akt requires phosphoinositide 3-kinase (PI 3-kinase) to

A)activate the RTK.
B)create phosphorylated lipids that serve as docking sites that localize Akt to the plasma membrane.
C)directly phosphorylate Akt.
D)create DAG.

Question 37

Which of the following mechanisms is NOT directly involved in inactivating an activated RTK?

A)dephosphorylation by serine/threonine phosphatases
B)dephosphorylation by protein tyrosine phosphatases
C)removal of the RTK from the plasma membrane by endocytosis
D)digestion of the RTK in lysosomes

Question 38

Akt promotes the survival of many cells by affecting the activity of Bad and Bcl2, as diagrammed in Figure 16-28. Figure 16-28
Which of the following statements is FALSE?

A)In the presence of a survival signal, Akt is phosphorylated.
B)In the absence of a survival signal, Bad inhibits the cell-death inhibitor protein Bcl2.
C)In the presence of a survival signal, the cell-death inhibitory protein Bcl2 is active.
D)In the absence of a survival signal, Bad is phosphorylated.

Question 39

When the cytosolic tail of the __________ receptor is cleaved, it migrates to the nucleus and affects gene regulation.

A)nuclear
B)Notch
C)growth factor
D)G-protein coupled

Question 40

The growth factor RGF stimulates proliferation of cultured rat cells.The receptor that binds RGF is a receptor tyrosine kinase called RGFR.Which of the following types of alteration would be most likely to prevent receptor dimerization?

A)a mutation that increases the affinity of RGFR for RGF
B)a mutation that prevents RGFR from binding to RGF
C)changing the tyrosines that are normally phosphorylated on RGFR dimerization to alanines
D)changing the tyrosines that are normally phosphorylated on RGFR dimerization to glutamic acid

Question 41

Name the three main classes of cell-surface receptor.

Question 42

Can signaling via a steroid hormone receptor lead to amplification of the original signal? If so, how?

Question 43

Nuclear receptors have binding sites for a signaling molecule and a DNA sequence.How is it that the same nuclear receptor, which binds to a specific DNA sequence, can regulate different genes in different cell types?

Question 44

For each of the following sentences, fill in the blanks with the best word or phrase selected from the list below.Not all words or phrases will be used; each word or phrase should be used only once.
cyclic GMP IGF NO
Delta IP₃ phosphodiesterase
diacylglycerol MAP kinase Ras
Cells signal to one another in various ways.Some use extracellular signal molecules that are dissolved gases, such as __________ which can diffuse easily into cells.Most receptor tyrosine kinases activate __________ , a small GTP-binding protein found at the cytosolic face of the plasma membrane.Some intracellular signaling pathways involve a series of protein kinases that phosphorylate each other, as seen in the __________ signaling module.Lipids can also relay signals in the cell, as we observe when phospholipase C cleaves the sugar-phosphate head off a lipid molecule to generate the two small messenger molecules __________ (which remains embedded in the plasma membrane) and __________ (which diffuses into the cytosol).

Question 45

Two protein kinases, PK1 and PK2, work sequentially in an intracellular signaling pathway.You create cells that contain inactivating mutations in the genes that encode either PK1 or PK2 and find that these cells no longer respond to a particular extracellular signal.You also create cells containing a version of PK1 that is permanently active and find that the cells behave as though they are receiving the signal even when the signal is not present.When you introduce the permanently active version of PK1 into cells that have an inactivating mutation in PK2, you find that these cells also behave as though they are receiving the signal even when no signal is present.
A.From these results, does PK1 activate PK2, or does PK2 activate PK1? Explain your answer.
B.You now create a permanently active version of PK2 and find that cells containing this version behave as though they are receiving the signal even when the signal is not present.What do you predict will happen if you introduce the permanently active version of PK2 into cells that have an inactivating mutation in PK1?

Question 46

For each of the following sentences, select the best word or phrase from the list below to fill in the blanks.Not all words or phrases will be used; each word or phrase should be used only once.
acetylase decouple GTP-binding
AMP-binding decrease neurotransmitter
amplify effector protein kinases
autocrine esterases protein phosphatases
cleavage integrate receptors
convolute GMP-binding sterols
An extracellular signal molecule can act to change a cell's behavior by acting through cell-surface __________ that control intracellular signaling proteins.These intracellular signaling proteins ultimately change the activity of __________ proteins that bring about cell responses.Intracellular signaling proteins can __________ the signal received to evoke a strong response from just a few extracellular signal molecules.A cell that receives more than one extracellular signal at the same time can __________ this information using intracellular signaling proteins.__________ proteins can act as molecular switches, letting a cell know that a signal has been received.Enzymes that phosphorylate proteins, termed __________, can also serve as molecular switches; the actions of these enzymes are countered by the activity of __________.

Question 47

For each of the following sentences, select the best word or phrase from the list below to fill in the blanks.Not all words or phrases will be used; each word or phrase should be used only once.
adenylyl cyclase cholera toxin GTPase
AMP diacylglycerol phosphodiesterase
ATP five seven
ATPase four three
Ca²⁺ GDP twelve
cAMP GTP two
G-protein-coupled receptors (GPCRs) all have a similar structure with __________ transmembrane domains.When a GPCR binds an extracellular signal, an intracellular G protein, composed of __________ subunits, becomes activated.__________ of the G-protein subunits are tethered to the plasma membrane by short lipid tails.When unstimulated, the α subunit is bound to __________ which is exchanged for __________ on stimulation.The __________ activity of the α subunit is important for inactivating the G protein.__________ inhibits this activity of the α subunit, thereby keeping the subunit in an active state.

Question 48

When the neurotransmitter acetylcholine is applied to skeletal muscle cells, it binds the acetylcholine receptor and causes the muscle cells to contract.Succinylcholine, which is a chemical analog of acetylcholine, binds to the acetylcholine receptor on skeletal muscle cells but causes the muscle cells to relax; it is therefore often used by surgeons as a muscle relaxant.Propose a model for why succinylcholine causes muscle relaxation.What might be the mechanism to explain the different activities of acetylcholine and succinylcholine on the acetylcholine receptor?

Question 49

Activated GPCRs activate G proteins by reducing the strength of binding of GDP to the α subunit of the G protein, allowing GDP to dissociate and GTP (which is present at much higher concentrations in the cell than GDP) to bind in its place.How would the activity of a G protein be affected by a mutation that reduces the affinity of the α subunit for GDP without significantly changing its affinity for GTP?

Question 50

Indicate by writing "yes" or "no" whether amplification of a signal could occur at the particular steps described below.Explain your answers.
A.An extracellular signaling molecule binds and activates a GPCR.
B.The activated GPCRs cause Gα to separate from Gβ and Gγ.
C.Adenylyl cyclase produces cyclic AMP.
D.cAMP activates protein kinase A.
E.Protein kinase A phosphorylates target proteins.

Question 51

When activated by the extracellular signal protein platelet-derived growth factor (PDGF), the PDGF receptor phosphorylates itself on multiple tyrosines (as indicated in Figure 16-61A by the circled Ps; the numbers next to these Ps indicate the amino acid number of the tyrosine).These phosphorylated tyrosines serve as docking sites for proteins that interact with the activated PDGF receptor.These proteins are indicated in the figure, and include the proteins A, B, C, and D.One of the cell's responses to PDGF is an increase in DNA synthesis, which can be measured by the incorporation of radioactive thymidine into the DNA.
To determine which protein or proteins-A, B, C, or D-are responsible for the activation of DNA synthesis, you construct mutant versions of the PDGF receptor that retain one or more tyrosine phosphorylation sites.You express these mutant versions in cells that do not make their own PDGF receptor.In these cells, the various mutant versions of the PDGF receptor are expressed normally, and, in response to PDGF binding, become phosphorylated on whichever tyrosines remain.You measure the level of DNA synthesis in cells that express the various mutant receptors and obtain the data shown in Figure 16-22B.
Figure 16-22
A.From these data, which, if any, of proteins A, B, C, and D are involved in the stimulation of DNA synthesis by PDGF? Explain your answer.
B.Which, if any, of these proteins inhibit DNA synthesis? Explain your answer.
C.Which, if any, of these proteins seem to have no detectable role in DNA synthesis? Explain your answer.

Question 52

Antibodies are Y-shaped molecules that have two identical binding sites.Suppose that you have obtained an antibody that is specific for the extracellular domain of an RTK.When the antibody binds to the RTK, it brings together two RTK molecules.If cells containing the RTK were exposed to the antibody, would you expect the kinase to be activated, inactivated, or unaffected? Explain your reasoning.

Question 53

Acetylcholine acts at a GPCR on heart muscle to make the heart beat more slowly.It does so by ultimately opening K⁺ channels in the plasma membrane (as diagrammed in Figure 16-51), which decreases the cell's excitability by making it harder to depolarize the plasma membrane.
Indicate whether each of the following conditions would increase or decrease the effect of acetylcholine.
A.addition of a drug that stimulates the GTPase activity of the Gα subunit
B.mutations in the K⁺ channel that keep it closed all the time
C.modification of the Gα subunit by cholera toxin
D.a mutation that decreases the affinity of the βγ complex of the G protein for the K⁺ channel
E.a mutation in the acetylcholine receptor that prevents its localization on the cell surface
F.adding acetylcholinesterase to the external environment of the cell

Question 54

Bacteria undergo chemotaxis toward amino acids, which usually indicates the presence of a food source.Chemotaxis receptors bind a particular amino acid and cause changes in the bacterial cell that induce the cell to move toward the source of the amino acid.Four types of chemotaxis receptor that mediate responses to different amino acids have been identified in a bacterium.The receptors are called ChrA, ChrB, ChrC, and ChrD.Each receptor specifically senses serine, aspartate, glutamate, or glycine, although you do not know which receptor senses which amino acid.You have been given a wild-type bacterial strain that contains all four receptors, as well as various mutant bacterial strains that are lacking one or more of the receptors.To figure out which receptor senses which amino acid, you conduct experiments in which you fill a capillary tube with an amino acid to attract the bacteria, dip the capillary tube into a solution containing bacteria, remove the capillary tube after 5 minutes, and count the number of bacteria in the capillary tube.Your results are shown in Table 16-26.
Table 16-26
From these results, indicate which receptor is used for which amino acid.

Question 55

You are interested in cell-size regulation and discover that signaling through an enzyme-coupled receptor is important for the growth (enlargement) of mouse liver cells.Activation of the receptor activates adenylyl cyclase, which ultimately leads to the activation of PKA, which then phosphorylates a transcription factor called TFS on threonine 42.This phosphorylation is necessary for the binding of TFS to its specific sites on DNA, where it then activates the transcription of Sze2, a gene that encodes a protein important for liver cell growth.You find that liver cells lacking the receptor are 15% smaller than normal cells, whereas cells that express a constitutively activated version of PKA are 15% larger than normal liver cells.Given these results, predict whether you would expect the cell's size to be bigger or smaller than normal cells if cells were treated in the following fashion.
A.You change threonine 42 on TFS to an alanine residue.
B.You create a version of the receptor that is constitutively active.
C.You add a drug that inhibits adenylyl cyclase.
D.You add a drug that increases the activity of cyclic AMP phosphodiesterase.
E.You mutate the cAMP-binding sites in the regulatory subunits of PKA, so that the complex binds cAMP more tightly.

Question 56

The rod photoreceptors in the eye are extremely sensitive to light.The cells sense light through a signal transduction cascade involving light activation of a GPCR that activates a G protein that activates cyclic GMP phosphodiesterase.How would you expect the addition of the following drugs to affect the light-sensing ability of the rod cells? Explain your answers.
A.a drug that inhibits cyclic GMP phosphodiesterase
B.a drug that is a nonhydrolyzable analog of GTP

Question 57

For each of the following sentences, fill in the blanks with the best word or phrase selected from the list below.Not all words or phrases will be used; each word or phrase should be used only once.
adenylyl cyclase endoplasmic reticulum nuclear
average extracellular peroxisome
Ca²⁺ high phospholipase C
calmodulin intracellular protein kinase A
colorful low protein kinase C
Ca²⁺ can trigger biological effects in cells because an unstimulated cell has an extremely __________ concentration of free Ca²⁺ in the cytosol, compared with its concentration in the __________ space and in the __________ creating a steep electrochemical gradient.When Ca²⁺ enters the cytosol, it interacts with Ca²⁺-responsive proteins such as __________ which also binds diacylglycerol, and __________ which activates CaM-kinases.

Question 58

When adrenaline binds to adrenergic receptors on the surface of a muscle cell, it activates a G protein, initiating an intracellular signaling pathway in which the activated ? subunit activates adenylyl cyclase, thereby increasing cAMP levels in the cell.The cAMP molecules then activate a cAMP-dependent kinase (PKA) that, in turn, activates enzymes that result in the breakdown of muscle glycogen, thus lowering glycogen levels.You obtain muscle cells that are defective in various components of the signaling pathway.Referring to Figure 16-20, indicate how glycogen levels would be affected in the presence of adrenaline in the following cells.Would they be higher or lower than in normal cells treated with adrenaline?
A.cells that lack adenylyl cyclase
B.cells that lack the GPCR
C.cells that lack cAMP phosphodiesterase
D.cells that have an ? subunit that cannot hydrolyze GTP but can interact properly with the ? and ? subunits

Question 59

Your friend is studying mouse fur color and has isolated the GPCR responsible for determining its color, as well as the extracellular signal that activates the receptor.She finds that, on addition of the signal to pigment cells (cells that produce the pigment determining fur color), cAMP levels rise in the cell.She starts a biotech company, and the company isolates more components of the signaling pathway responsible for fur color.Using transgenic mouse technology, the company genetically engineers mice that are defective in various proteins involved in determining fur color.The company obtains the following results.
• Normal mice have beige (very light brown) fur color.
• Mice lacking the extracellular signal have white fur.
• Mice lacking the GPCR have white fur.
• Mice lacking cAMP phosphodiesterase have dark brown fur.
Your friend has also made mice that are defective in the α subunit of the G protein in this signaling pathway.The defective α subunit works normally except that, once it binds GTP, it cannot hydrolyze GTP to GDP.What color do you predict that the fur of these mice will be? Why?

Question 60

A calmodulin-regulated kinase (CaM-kinase) is involved in spatial learning and memory.This kinase is able to phosphorylate itself such that its kinase activity is now independent of the intracellular concentration of Ca²⁺.Thus, the kinase stays active after Ca²⁺ levels have dropped.Mice completely lacking this CaM-kinase have severe spatial learning defects but are otherwise normal.
A.Each of the following mutations also leads to similar learning defects.For each case explain why.
(1) a mutation that prevents the kinase from binding ATP
(2) a mutation that deletes the calmodulin-binding part of the kinase
(3) a mutation that destroys the site of autophosphorylation
B.What would be the effect on the activity of CaM-kinase if there were a mutation that reduced its interaction with the protein phosphatase responsible for inactivating the kinase?