Chapter 16: Cell Signaling

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

d. the different classes of GPCR ligands (proteins, amino acid derivatives, or fatty acids) bind to receptors with different numbers of transmembrane domains

Enzyme-coupled receptors

discovered for this role in responding to growth factors in animal cells

Ion channeled coupled receptors

alter the membrane potential directly by changing the permeability of the plasma membrane

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

A. changes in cell secretion B. changes in protein phosphorylation C. changes in membrane potential

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

Because the interactions of the signal molecule with its receptor and of the activated receptor with its gene are both one-to-one, there is no amplification in this part of the signaling pathway. The signal can, however, be amplified when the target genes are transcribed, because each activated gene produces multiple copies of mRNA, each of#which is used to make multiple copies of the protein that the gene encodes.

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

The neurotransmitter released from a neuron in neuronal signaling must diffuse across the synaptic cleft to reach receptors on the target cell. In contrast, in contact- dependent signaling, the signal molecule is attached to the plasma membrane of the signaling cell and interacts with receptors located on the plasma membrane of the receiving cell; thus, the cells must be in direct contact for this type of signaling to occur.

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 gland cells, and skeletal muscle cells all express an acetylcholine receptor that belongs to the transmitter-gated ion channel family

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

adenylyl cyclase

increases in cAMP levels

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

b. Notch

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.

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

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. 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.

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.

b. The regulation of inflammatory responses at the site of an infection is an example of paracrine signaling

Figure 16-34 shows that intracellular signaling pathways can be highly interconnected. 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.

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 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.

c. QGF activates different intracellular signaling pathways in heart muscle cells, fibroblasts, and nerve cells produce the different responses observed

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 β complex.

c. The α subunit exchanges its bound GDP for GTP

phospholipase C

cleavage of inositol phospholipids

Name the three main classes of cell- surface receptor.

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

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.

A. Any answer that involves the modification of existing cell components is correct. Protein phosphorylation, protein dephosphorylation, protein ubiquitylation, lipid phosphorylation, and lipid cleavage are all examples of correct answers. B. Responses that involve alterations in gene expression occur slowly. C. Modification of existing cell components can happen quickly, whereas responses that depend on changes in gene expression take much longer because the genes will need to be transcribed, the mRNAs will need to be translated, and the proteins need to accumulate to high- enough levels to instigate change.

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?

Although succinylcholine can bind to the acetylcholine receptor, it does not activate the receptor and therefore does not cause the muscle cell to contract. Instead, succinylcholine blocks the ability of acetylcholine to bind to the receptor and thereby prevents acetylcholine from stimulating muscle contraction.

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.

Smallest to largest: * Contact-dependent signaling, * Neuronal signaling, * Paracrine signaling * Endocrine signaling

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.

a. The cells you create will divide less frequently than normal cells in response to the extracellular signals that typically activate Ras.

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. 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.

a. When the transcriptional regulator is phosphorylated, it activates transcription of the ethylene-responsive genes.

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

a. addition of a drug that causes cyclic AMP phosphodiesterase to be hyperactive

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? 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

a. addition of a high concentration of a nonhydrolyzable analog of GTP

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 serine/threonine phosphatases

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? 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

G-protein-coupled receptors

all receptors of this class are polypeptides with seven transmembrane domains

ion channels

changes in membrane potential

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

b. The β subunit activates the mating response but is inhibited when bound to α.

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? 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 it 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 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

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. 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

b. addition of TRK ligand and a drug that inhibits the activity of the phosphatase that acts on SZE

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.

b. create phosphorylated lipids that serve as docking sites that

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.

b. hormone

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? 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 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? 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

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

c. interacting with cell-surface receptors, causing the receptors to transduce signal inappropriately in the absence of the normal stimulus

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

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. 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.

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

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.

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 Gβ. d. GTPase activity of Gα.

d. GTPase activity of Gα.

Akt promotes the survival of many cells by affecting the activity of Bad and Bcl2, as diagrammed in 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.

d. In the absence of a survival signal, Bad is phosphorylated.

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

d. contact-dependent

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.

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