Chapter 16 Cell Communication

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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.

create phosphorylated lipids that serve as docking sites that localize Akt to the plasma membrane.

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.

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

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.

The α subunit exchanges its bound GDP for GTP.

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 βγ. ​b.​The βγ subunit activates the mating response but is inhibited when bound to α. ​c.​The G protein is inactive; either the 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.

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

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.

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.

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.

Extracellular signal molecules that are hydrophilic must bind to a cell-surface receptor so as to signal a target cell to change its behavior.

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

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.

PI 3-kinase phosphorylates a lipid in the plasma membrane. MAP kinases are phosphorylated by MAP kinase kinases. Ras exchanges its GDP for GTP when activated. GPCRs do not dimerize upon ligand binding.

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.

Phosphatases remove the phosphate from GTP on GTP-binding proteins, turning them off.

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.

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

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

addition of a drug that causes cyclic AMP

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.

hormone

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.

interact with signal molecules that diffuse through the plasma membrane.

​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.

is activated by two or more proteins in different signaling pathways.

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

contact-dependent

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

A.​Decrease. An increase in the GTPase activity of the Gα subunit will decrease the length of time that the G protein is active. ​B.​Decrease. If the K+ channel remains closed, acetylcholine will not slow the heart. ​C.​Increase. Cholera toxin inhibits the GTPase activity of the Gα subunit, keeping the subunit in an active state for a longer time. ​D.​Decrease. The activated βγ complex binds to and activates the K+ channel; decreasing their affinity for each other will decrease the time that the K+ channel is open, effectively decreasing the effect of acetylcholine. ​E.​Decrease. If there is no receptor on the cell surface, cells will be unable to respond to acetylcholine. ​F.​Decrease. Acetylcholinesterase degrades acetylcholine and thus will decrease the effect of acetylcholine.

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. Each signaling molecule activates only one receptor molecule. ​B.​Yes. Each activated GPCR activates many G-protein molecules. ​C.​Yes. Each activated adenylyl cyclase molecule can generate many molecules of cAMP. ​D.​No. In unstimulated cells, protein kinase A is held inactive in a protein complex. Binding of cAMP to the complex induces a conformational change, releasing the active protein kinase A. Therefore, one cAMP cannot activate more than one molecule of protein kinase A. ​E.​Yes. Each activated protein kinase A molecule can phosphorylate many molecules of each type of target protein.

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 __________.

An extracellular signal molecule can act to change a cell's behavior by acting through cell-surface receptors that control intracellular signaling proteins. These intracellular signaling proteins ultimately change the activity of effector proteins that bring about cell responses. Intracellular signaling proteins can amplify 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 integrate this information using intracellular signaling proteins. GTP-binding proteins can act as molecular switches, letting a cell know that a signal has been received. Enzymes that phosphorylate proteins, termed protein kinases, can also serve as molecular switches; the actions of these enzymes are countered by the activity of protein phosphatases.

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.

Ca2+ can trigger biological effects in cells because an unstimulated cell has an extremely low concentration of free Ca2+ in the cytosol, compared with its concentration in the extracellular space and in the endoplasmic reticulum, creating a steep electrochemical gradient. When Ca2+ enters the cytosol, it interacts with Ca2+-responsive proteins such as protein kinase C, which also binds diacylglycerol, and calmodulin, which activates CaM-kinases.

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.

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

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.

G-protein-coupled receptors (GPCRs) all have a similar structure with seven transmembrane domains. When a GPCR binds an extracellular signal, an intracellular G protein, composed of three subunits, becomes activated. Two of the G-protein subunits are tethered to the plasma membrane by short lipid tails. When unstimulated, the α subunit is bound to GDP, which is exchanged for GTP on stimulation. The intrinsic GTPase activity of the α subunit is important for inactivating the G protein. Cholera toxin inhibits this activity of the α subunit, thereby keeping the subunit in an active state.

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.

GTPase activity of Gα.

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.

Heart muscle cells, salivary gland cells, 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 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.

Receptor R binds to factor F to induce cell proliferation in cell line A.

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

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

​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

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

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

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

a mutation that prevents RGFR from binding to RGF

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

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

addition of a high concentration of a nonhydrolyzable analog of GTP

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 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

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


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