Molecular Bio Chapter 16

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.

(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.

Match the target of the G protein with the appropriate signaling outcome. adenylyl cyclase ____1____ ion channels ____2_____ phospholipase C ____3_____ A. cleavage of inositol phospholipids B. increase in cAMP levels C. changes in membrane potential

1) B 2) C 3) A

Name the three main classes of cell-surface receptor.

1. ion-channel-linked receptors 2. G-protein linked receptors 3. enzyme-linked receptors

Given the generic signaling pathway in Figure Q16-9, write the number corresponding to the item on the line next to the descriptor below. _________ receptor protein _________ effector proteins _________ intracellular signaling proteins _________ ligand

2,4,3,1

Rank the following types of cell signaling from 1 to 4, with 1 representing the type of signaling in which the signal molecule travels the least distance and 4 the type of signaling in which the signal molecule travels the largest distance. ______ paracrine signaling ______ contact-dependent signaling ______ neuronal signaling ______ endocrine signaling

3,1,2,4

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?

A) 1. Protein kinases have a binding site for ATP, which is the source of the phosphate used for phosphoylating their target proteins. If the kinase cannot bind ATP, it will be inactive. 2. Because binding to calmodulin in the presence of Ca2+ activates CaM-kinases, deletion of the calmodulin binding portion would inactivate the kinase 3. A mutation that destroys the site of autophosphorylation will also impair the normal function of the kinase, because the kinase will become inactive as soon as Ca2+ levels decrease. B) The kinase would stay active for longer after a transient increase in intracellular Ca2+ concentration.

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. Cells signal to one another in various ways. Some use extracellular signal molecules that are dissolved gases, such as _______A___________, which can diffuse easily into cells. Others use cytokines, which bind to cytokine receptors. Cytokine receptors have no intrinsic enzyme activity but are associated with cytoplasmic tyrosine kinases called _________B_________s, which become activated on the binding of cytokine to its receptor and go on to phosphorylate and activate cytoplasmic transcriptional regulators called _______C___________s. Some intracellular signaling pathways involve chains of protein kinases that phosphorylate each other, as seen in the ______D____________ 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 ______E____________ (which remains embedded in the plasma membrane) and ______F____________ (which diffuses into the cytosol). cyclic GMP MAP kinase STAT diacylglycerol NO TGF-β IP3 Ras JAK SMAD

A) NO B) JAK C) STAT D) MAP kinase E) diacylglycerol F) IP3

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?

A) Normally PK2 activates PK1. If PK1 is permanently activated, a response is seen independently of whether or not PK2 is present. B) You would predict that no response to the signal would be observed. PK2 usually needs to activate PK1 for the cells to respond to the signal. When PK2 is permanently activated in the absence of PK1, PK1 is not there to relay the signal.

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 Q16-25), 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

A) decrease B) decrease C) increase D) decrease E) decrease F) decrease

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. Cells can signal to each other in various ways. A signal that must be relayed to the entire body is most efficiently sent by _________A_________ cells, which produce hormones that are carried throughout the body through the bloodstream. On the other hand, _______B___________ methods of cell signaling do not require the release of a secreted molecule and are used for very localized signaling events. During _____C_____________ signaling, the signal remains in the neighborhood of the secreting cell and thus acts as a local mediator on nearby cells. Finally, _______D___________ signaling converts electrical impulses into a chemical signal. Cells receive signals through a _________E_________, which can be an integral membrane protein or can reside inside the cell. amplification G-protein phosphorylation contact-dependent K+ channel receptor endocrine neuronal target epithelial paracrine

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

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 α 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 Q16-29, 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 α subunit that cannot hydrolyze GTP but can interact properly with the β and γ subunits

A) higher B) higher C) lower D) lower

Receipt of extracellular signals can change cell behavior quickly (e.g., in seconds or less) or much more slowly (e.g., in hours). A. What kind of molecular changes could cause quick changes in cell behaviour? B. What kind of molecular changes could cause slow changes in cell behaviour? 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.

A) ion channels opening, phosphorylation B) changes in gene expression C) changes in gene expression take longer because they must undergo transcription and translation

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.

A) no B) yes C) yes D) no E) yes

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. An extracellular signal molecule can act to change a cell's behavior by acting through cell-surface ______A____________ that control intracellular signaling proteins. These intracellular signaling proteins ultimately change the activity of ________B__________ proteins that bring about cell responses. Intracellular signaling proteins can ________C__________ 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 a time can ____D____ this information using intracellular signaling proteins. ______E___________ proteins can act as molecular switches, letting a cell know that a signal has been received. Enzymes that phosphorylate proteins, termed ___F________, can also serve as molecular switches; the actions of these enzymes are countered by the activity of ___G_______________. GMP-binding effector cleavage GTP-binding decrease decouple protein phosphatases esterases sterols neurotransmitter integrate convolute amplify AMP-binding protein kinases acetylase receptors autocrine

A) receptors B) effector C) amplify D) integrate E) GTP-binding F) protein kinases G) protein phosphatases

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. G-protein-coupled receptors (GPCRs) all have a similar structure with ______A____________ transmembrane domains. When a GPCR binds an extracellular signal, an intracellular G protein, composed of _________B_________ subunits, becomes activated. ________C__________ of the G-protein subunits are tethered to the plasma membrane by short lipid tails. When unstimulated, the α subunit is bound to ______D____________, which is exchanged for _______E___________ on stimulation. The intrinsic ________F__________ activity of the α subunit is important for inactivating the G protein. _______G___________ inhibits this activity of the α subunit, thereby keeping the subunit in an active state. phosphodiesterase five ATP GTP adenylyl cyclase GTPase seven cholera toxin Ca2+ four AMP twelve GDP cAMP diacylglycerol three ATPase two

A) seven B) three C) two D) GDP E) GTP F) GTPase G) cholera

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.

A) smaller B) larger C) smaller D) smaller E) larger

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

A) this drug would lead to the photoreceptor always signaling that it has not absorbed a photon B) this would lead the the photoreceptor always signaling it has absorbed a photon

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. Ca2+ can trigger biological effects in cells because an unstimulated cell has an extremely _______A___________ concentration of free Ca2+ in the cytosol, compared with its concentration in the ______B____________ space and in the ______C____________, creating a steep electrochemical gradient. When Ca2+ enters the cytosol, it interacts with Ca2+-responsive proteins such as ______D____________, which also binds diacylglycerol, and ________E__________, which activates CaM-kinases. average extracellular nuclear phosopholipase C protein kinase C low peroxisome high Ca2+ adenylyl cyclase protein kinase A intracellular endoplasmic reticulum calmodulin colorful

A)A) low B) extracellular C) endoplasmic reticulum D) protein kinase C E) calmodulin

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

Since the interactions of the signal molecule with its receptor and of the activated receptor with the regulatory region of a target gene are both one-to-one, there is no amplification. The signal can be amplified with the target gene is transcribed, since multiple copies of mRNA are usually produced from a gene once it has been switched on, and multiple copies of protein can be made from each mRNA molecule.

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

Steroid hormone receptors, after binding to a specific DNA sequence, can set off primary and secondary response proteins, activating and deactivating different portions of DNA transcription, resulting in differing regulation in different cell types.

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.

The RTK will probably become activated on binding of the antibody molecule. This is because signal-induced dimerization usually activates RTKs. When RTK molecules are brought together, their cytoplasmic kinase domains become activated and each receptor phosphorylates the other.

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?

The mice with defective alpha subunit should have white fur. We can see that any block in signal due to absence of extracellular signal or defective GPCR lead to mice with white fur. Thus, with defective G-protein the signal will be blocked. If the signal is not regulated, the synthesis of the some pigment protein becomes constituitive and that results in dark brown fur.

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?

The mutant G protein would be constantly active. Each time the subunit hydrolyzed GTP to GDP, the GDP would dissociate, allowing GTP to bind and reactivate the subunit. Normally, GDP is tightly bound by the subunit. Normally, GDP is tightly bound by the subunit, keeping the G protein in its inactive state until release of GDP is stimulated by interactions with an appropriate activated G-protein-linked receptor.

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 Q16-25. Which of the following would enhance this effect of the acetylcholine? (a) addition of a high concentration of a non-hydrolyzable 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

a) addition of a high concentration of a non-hydrolyzable analog of GTP

Circle 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

a) changes in cell secretion b) changes in protein phosphorylation c) changes in membrane potential

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

a) dephosphorylation by serin/.threonine phosphataes

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.

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

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.

a) phosphatases remove the phosphate from GTP on GTP-binding proteins, turning them off

Activated protein kinase C (PKC) can lead to the modification of the membrane lipids in the vicinity of the active PKC. Figure Q16-30 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? (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

a) the expression of a constitutively active phospholipase C

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 response genes (see Fig. Q16-50). You discover a phosphatase that is important for ethylene signaling, and you name it PtpE. Plants lacking PtpE never turn on ethylene-response 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. Which of the following statements below is inconsistent with your data? (a) When the transcriptional regulator is phosphorylated, it activates transcription of the ethylene-response 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.

a) when the transcriptional regulator is phosphorylated, it activates transcription of the ethylene-response genes.

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) STAT proteins phosphorylate JAK proteins, which then enter the nucleus and activate gene transcription.

b) PI 3-kinase phosphorylates a lipid in the plasma membrane

Figure Q16-15 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? (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

b) a muscle cell that has a defect in guanylyl cyclase such that is constitutively converts GTP to cyclic GMP

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 to RGF 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

b) a mutation that prevents RGFR from binding to RGF

Male cockroaches with mutations that strongly decrease the function of an RTK called RTKX are oblivious to the charms of their female comrades. This particular RTK binds to a small molecule secreted by sexually mature females. Most males carrying loss-of-function mutations in the gene for Ras protein are also unable to respond to females. You have just read a paper in which the authors describe how they have screened cockroaches that are mutant in RTKX for additional mutations that partly restore the ability of males to respond to females. These mutations decrease the function of a protein that the authors call Z. Which of the following types of protein could Z be? Explain your answer. (a) a protein that activates the Ras protein by causing Ras to exchange GDP for GTP (b) a protein that stimulates hydrolysis of GTP by the Ras protein (c) an adaptor protein that mediates the binding of the RTKX to the Ras protein (d) a transcriptional regulator required for the expression of the Ras gene

b) a protein that stimulates hydrolysis of GTP by the Ras protein

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.

b) heart muscle cells, salivary glands, and skeletal muscle cells all express an acetylcholine receptor that belongs to the transmitter-gated ion channel family

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 Q16-1. 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.

b) receptor R binds to Factor F to induce cell proliferation in cell line A

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 16-27. Which of the following models is consistent with the data from the analysis of these mutants? Explain your answer. (a) α activates the mating response but is inhibited when bound to βγ. (b) βγ activates the mating response but is inhibited when bound to α. (c) The G protein is inactive; either free α or free βγ complex is capable of activating the mating response. (d) The G protein is active; both free α and free βγ complex are required to inhibit the mating response

b) βγ activates the mating response but is inhibited when bound to a

Figure Q16-51 shows that intracellular signaling pathways can be highly interconnected. From the information in Figure Q16-51, which of the following statements is incorrect? (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.

c) CaM-kinase is only activated when the GPCR is active and not when the RTK is active

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 muscles, 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 GQF.

c) QGF activates different intracellular signaling pathways in heart muscles, fibroblasts, and nerve cells to produce the different responses observed

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 Q16-28. 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? (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

c) a mutation in the gene that encodes cAMP phosphodiesterase that makes the enzyme inactive

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

c) a mutation that inactivates the protein tyrosine phosphatase that normally removes the phosphates from tyrosines on the activated receptor

Figure Q16-52 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? (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

c) addition of a drug that blocks protein Y from interacting with its target

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

c) diffusing into cells and stimulating the cyclase directly

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

c) is activated by two or more proteins in different signaling pathways

The following happens when a cell-surface 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.

c) the a subunit exchanges its bound GDP for GTP

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 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?

conformation states of the receptor alter ion flow

Adrenaline stimulates glycogen breakdown in skeletal muscle cells by ultimately activating glycogen phosphorylase, the enzyme that breaks down glycogen, as depicted in Figure Q16-29. Which of the following statements below 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.

d) a constitutively active mutant form of PKA in skeletal muscle cells would lead to an excess in the amount of glycogen available

Akt promotes the survival of many cells. It is activated by an intracellular signaling pathway that is triggered by an RTK that activates PI 3-kinase, as diagrammed in Figure Q16-48. Which of the following statements is false? (a) In the presence of a survival signal, Akt localizes to the plasma membrane by binding to PIP3. (b) In the absence of survival signal, Bad inhibits the cell death inhibitor protein Bcl2. (c) In the presence of survival signal, the cell death inhibitory protein Bcl2 is active. (d) In the absence of survival signal, Bad is phosphorylated.

d) in the absence of survival signal, Bad is phosphorylated

All members of the steroid hormone 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

d) interact with signal molecules that diffuse through the plasma membrane