Chapter 16 Cell Signaling questions
16-22 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)
16-32 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 Q16-32. 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)
16-38 Activated protein kinase C (PKC) can lead to the modification of the membrane lipids in the vicinity of the active PKC. Figure Q16-38 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)
16-40 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)
16-49 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)
16-26 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), either block or overstimulate the receptor's natural activity
16-23 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), removes the phosphate from switch proteins
16-18 Figure Q16-18 shows the pathway through which nitric oxide (NO) triggers smooth muscle relaxation in a blood-vessel wall. Which of the following situations would lead to relaxation of the smooth muscle cells in the absence of acetylcholine? Figure Q16-18 (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)
16-46 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)
16-57 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) to create DAG.
(b)
16-7 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)
16-15 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 and salivary gland cells have receptor proteins, whereas skeletal muscles have a different receptor protein
16-54 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), These phosphorylated lipids serve as docking sites for specific intracellular signaling proteins, which relocate from the cytosol to the plasma membrane, where they can activate one another.
16-5 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), hormones are the most "public" style of cell-to-cell communication involves broadcasting the signal throughout the whole body by secreting it into the bloodstream, and these are the extracellular molecules that perform this
16-11 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)
16-13 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)
16-17 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)
16-35 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 Q16-35. 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)
16-45 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)
16-31 The length of time a G protein will signal is determined by _______. (a) the activity of phosphatases that turn off G proteins by dephosphorylating Gα. (b) the activity of phosphatases that turn GTP into GDP. (c) the degradation of the G protein after Gαseparates from Gβγ (d) the GTPase activity of Gα
(d)
16-36 Adrenaline stimulates glycogen breakdown in skeletal muscle cells by ultimately activating glycogen phosphorylase, the enzyme that breaks down glycogen, as depicted in Figure Q16-36. 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)
16-6 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)
16-10 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), NO binds to and activates the target protein guanylyl cyclase, which ends up catalyzing production of cyclic GMP from GTP; regulating the activity of specific proteins to cause smooth muscle cells to relax
16-30 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.)
16-20 Name the three main classes of cell-surface receptor.
1. Ion-channel-coupled receptors - change the permeability of the plasma membrane to selected ions, thereby altering the membrane potential and possibly producing an electrical current 2. G-protein-coupled receptors - Activate membrane-bound, trimeric GTP-binding proteins (G proteins), when then activate or inhibit an enzyme or an ion channel in the plasma membrane, initiating an intracellular signaling cascade 3. Enzyme-coupled receptors - Either act as enzymes or associate with enzymes inside the cell. When stimulated, the enzymes can activate a wide variety of intracellular signaling pathways
16-39 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) CaM-kinase will be inactive without any ATP to bind to, the molecule it needs for phosphorylation of target protein 2) Calcium will not be able to bind to calmodulin, rendering it inactive 3)Without being able to phosphorylate itself, the kinase will only be active with the intracellular concentration of Ca2+ levels B. The CaM-kinase will be able to influence other processes in the cell more freely, becoming more active
16-9 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. Changes in cell movement, secretion, metabolism. B. Changes in gene expression and the synthesis of new proteins, with cell growth and division C. A offers a quick change because the signal affects the activity of proteins already present inside the target cell, B is slow since the extracellular signals require changes in gene expression and the production of new proteins
16-42 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. There would be no sharp fall in the cytosolic concentration of cyclic GMP, so cation channels in the photoreceptor cell plasma membrane are kept open, and activated rhodopsin results in the activation of transducin α subunits which would usually turn of cyclic GMP phosphodiesterase. B. The drug would increase the light-sensing response
16-8 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
16-48 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
Activated, since the RTK molecules come together in the plasma membrane and form a dimer when binding of an extracellular signal like this antibody.
16-19 For each of the following sentences, select the best word or phrase from the list below to fill in the blanks. 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 ____________________ _______________________. 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 ___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 kinase______, can also serve as molecular switches; the actions of these enzymes are countered by the activity of _____protein phosphatases________.
16-2 For each of the following sentences, fill in the blanks with the best word or phrase selected from the list below. 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. 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 _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
16-24 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?
Each hormone binds to a different nuclear receptor, and each receptor acts at a different set of regulatory sites in DNA. A given hormone usually regulates different sets of genes in different cell types, thereby evoking different physiological responses in different target cells
16-21 Match the class of cell-surface receptor with the best description of its function. Not all descriptors will be used. G-protein-coupled receptors _____ ion-channel-coupled receptors _____ enzyme-coupled receptors ____ A. alter the membrane potential directly by changing the permeability of the plasma membrane B. signal by opening and closing in a ligand-independent manner C. must be coupled with intracellular monomeric GTP-binding proteins D. all receptors of this class are polypeptides with seven transmembrane domains E. discovered for their role in responding to growth factors in animal cells
G-protein-coupled receptors __C___ ion-channel-coupled receptors __A___ enzyme-coupled receptors __E__
16-27 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 __________________ 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 intrinsic __________________ 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. adenylyl cyclase cholera toxin GTPase AMP diacylglycerol phosphodiesterase ATP five seven ATPase four three Ca2+ GDP twelve cAMP GTP two
Seven Three Two alpha GDP GTP GTPase Cholera toxin
16-4 Explain why the signal molecules used in neuronal signaling work at a longer range than those used in contact- dependent signaling
The axon of a neuron terminates at synapses (specialized junctions) on target cells that can lie far from the neuronal cell body. When activated by signals from the environment or from other nerve cells, a neuron sends electrical impulses racing along its axon quickly. On reaching the axon terminal, these electrical signals are converted into a chemical: each electrical impulse stimulates the nerve terminal to release a pulse of an extracellular molecule called a neurotransmitter, which diffuses across the narrow gap that separates the membrane of the axon terminal from that of the target cell, reaching its destination super quickly. In cell-to-cell communication, the cells make direct physical contract through signal molecules lodged in the plasma membrane of the signaling cell and receptor proteins embedded in the plasma membrane of the target cell
16-41 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?
There would be no point of GPCRs in our mechanism, since the α subunit would constantly prefer binding to GTP by default. It would be constitutively active
16-3 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___ paracrine signaling __1___ contact-dependent signaling __2___ neuronal signaling __4___ endocrine signaling
16-12 Given the generic signaling pathway in Figure Q16-12, write the number corresponding to the item on the line next to the descriptor below. ________ receptor protein ________ effector proteins ________ intracellular signaling proteins ________ ligand
____2____ receptor protein ____4____ effector proteins ____3____ intracellular signaling proteins ____1____ ligand
16-43 Match the target of the G protein with the appropriate signaling outcome. adenylyl cyclase ________ ion channels _________ phosphospholipase C _______ A. cleavage of inositol phospholipids B. increase in cAMP levels C. changes in membrane potential
adenylyl cyclase ___B__ ion channels ____C_____ phosphospholipase C ___A____
16-44 For each of the following sentences, fill in the blanks with the best word or phrase selected from the list below. 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. adenylyl cyclase endoplasmic reticulum nuclear average extracellular peroxisome Ca2+ high phospholipase C calmodulin intracellular protein kinase A colorful low protein kinase C
low extracellular endoplasmic reticulum protein kinase C calmodulin