The correct answer is d B. Answer b is incorrect. Transcription factors are proteins that bind DNA and trigger a change in gene expression.

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1 1. What is a ligand? a. An integral membrane protein associated with G proteins b. A DNA-binding protein that alters gene expression c. A cytoplasmic second-messenger molecule d. A molecule or protein that can bind to a receptor A. Answer a is incorrect. Receptor proteins are integral membrane proteins. G proteincoupled receptors function through their association with G proteins. B. Answer b is incorrect. Transcription factors are proteins that bind DNA and trigger a change in gene expression. C. Answer c is incorrect. Second-messenger molecules are produced as a result of an initial ligand-receptor signaling event. A molecule or protein that can bind to a receptor D. Answer d is correct. Ligands are typically small molecules or proteins that travel through the extracellular environment and interact with cell-surface receptor proteins. 2. In the case of paracrine signaling the ligand is a. produced by the cell itself b. secreted by neighboring cells c. present on the plasma membrane of neighboring cells d. secreted by distant cells A. Answer a is incorrect. A signal produced by the cell itself is an example of autocrine signaling. secreted by neighboring cells B. Answer b is correct. Paracrine signaling is limited to the immediate cellular environment. C. Answer c is incorrect. Signaling through the interaction of membrane proteins is an example of direct contact signaling. D. Answer d is incorrect. When the origin of a ligand is distant from the site receptor binding, the signaling is said to be endocrine. 3. A neurotransmitter functions as a ligand in which type of signaling? a. Direct contact b. Endocrine c. Synaptic signaling d. Autocrine

2 A. Answer a is incorrect. Direct contact signaling requires that proteins on the surface of the two neighboring cells form a physical connection. B. Answer b is incorrect. Endocrine signaling requires that a physical distance exist between the cellular source of a ligand and the eventual site of ligand receptor binding. Synaptic signaling C. Answer c is correct. Synaptic signaling is a special type of signaling associated with the cells of the nervous system. A synapse is the small gap that exists between two nerve cells. Neurotransmitters diffuse across this small space. D. Answer d is incorrect. Autocrine signaling occurs when the cell creates its own signals. 4. The function of a is to add phosphates to proteins, whereas a functions to remove the phosphates. a. tyrosine; serine b. protein phosphatase; protein dephosphatase c. protein kinase; protein phosphatase d. receptor; ligand A. Answer a is incorrect. The amino acids tyrosine and serine are capable of being phosphorylated. They receive the phosphate group, but do not function in the process of phosphorylation. B. Answer b is incorrect. A phosphatase is an enzyme that removes phosphates. protein kinase; protein phosphatase C. Answer c is correct. A kinase is an enzyme that attaches a phosphate group to a protein, and a phosphatase removes phosphate groups. D. Answer d is incorrect. Some receptors can function to phosphorylate proteins; however, ligand molecules are not involved in the removal of phosphate group. 5. Which of the following type(s) of membrane receptors functions by changing the phosphorylation state of proteins in the cell? a. Channel-linked receptor b. Enzymatic receptor c. G protein-coupled receptor d. Both b and c A. Answer a is incorrect. A channel-linked receptor functions to allow the movement of ions into or out of a cell.

3 B. Answer b is incorrect. Enzymatic receptors can function as kinases, phosphorylating themselves and surrounding protein substrates. However, this is not the only true option. C. Answer c is incorrect. G protein-coupled receptors can activate signal transduction pathways that activate protein kinases. They activate PKA, PKC, and also can stimulate MAP kinase cascade. However, this is not the only true option. Both b and c D. Answer d is correct. Both enzymatic receptors and G protein-coupled receptors can activate protein kinases or phosphatases, and thus the phosphorylation state of a cell. 6. How does the function of an intracellular receptor differ from that of a membrane receptor? a. The intracellular receptor binds a ligand. b. The intracellular receptor binds DNA. c. The intracellular receptor activates a kinase. d. The intracellular receptor functions as a second messenger. A. Answer a is incorrect. All receptors must bind a ligand in order to function. The intracellular receptor binds DNA. B. Answer b is correct. Only the intracellular type of receptors is capable of directly binding to DNA in response to ligand binding. C. Answer c is incorrect. Enzymatic receptors present on the plasma membrane can function as kinases themselves, or can activate a signal cascade involving kinases. D. Answer d is incorrect. G protein-coupled receptors located in the plasma membrane of a cell function to trigger the production of second-messenger molecules. 7. During a protein kinase signal cascade a. sequential phosphorylation of different kinases leads to a change in gene expression b. multiple G proteins become activated c. phosphorylation of adapter proteins leads to the formation of second messengers d. the number of MAP kinase proteins present in the cytoplasm is amplified sequential phosphorylation of different kinases leads to a change in gene expression A. Answer a is correct. A signal cascade involves many different proteins that interact in a step-by-step pathway.

4 B. Answer b is incorrect. G proteins are associated with enzymes that catalyze the production of second-messenger molecules, not enzymes that phosphorylate proteins. C. Answer c is incorrect. Adaptor proteins are an important part of a protein kinase signal cascade, but they do not function to synthesize second-messenger molecules. D. Answer d is incorrect. The activity of MAP kinase proteins changes as part of the cascade; however, the number of proteins present in the cytoplasm does not. 8. What is the function of Ras during tyrosine kinase cell signaling? a. It activates the opening of channel-linked receptors. b. It synthesizes the formation of second messengers. c. It phosphorylates other enzymes as part of a pathway. d. It links the receptor protein to the MAP kinase pathway. A. Answer a is incorrect. The opening of a channel-linked receptor is controlled by ligand binding. B. Answer b is incorrect. G protein-regulated enzymes such as adenylyl cyclase are responsible for the synthesis of second-messenger molecules. C. Answer c is incorrect. Ras is not a kinase protein. It links the receptor protein to the MAP kinase pathway. D. Answer d is correct. Ras functions to activate the first kinase in the MAP kinase pathway. The activity of Ras is regulated by the tyrosine kinase receptor. 9. Which of the following best describes the immediate effect of ligand binding to a G protein-coupled receptor? a. The G protein trimer releases a GDP and binds a GTP. b. The G protein trimer dissociates from the receptor. c. The G protein trimer interacts with an effector protein. d. The α subunit of the G protein becomes phosphorylated. The correct answer a The G protein trimer releases a GDP and binds a GTP. A. Answer a is correct. Ligand binding to a G protein-coupled receptor results in the activation of the G protein. G proteins are only active when they bind a GTP molecule. The correct answer a B. Answer b is incorrect. The G protein trimer must be released from the receptor in order to function, but it first must bind a molecule of GTP. The correct answer a

5 C. Answer c is incorrect. G proteins can only interact with their effector proteins after they become activated and dissociate from the G protein-coupled receptor. The correct answer a D. Answer d is incorrect. The α subunit of the G protein can bind GTP; it does not become phosphorylated. 10. The amplification of a cellular signal requires all of the following except a. a ligand b. DNA c. a second messenger d. a protein kinase A. Answer a is incorrect. All signaling pathways require a ligand-binding event to start. Amplification cannot happen without ligand binding first. DNA B. Answer b is correct. DNA and changes in gene expression are typically the final step in a signaling pathway and not part of the amplification process. C. Answer c is incorrect. Second messengers are important for amplification because a single signaling event can result in the production of many second-messenger molecules. D. Answer d is incorrect. Protein kinases are involved in signal amplification through their ability to phosphorylate more than one substrate protein. 11. Adenylyl cyclase is responsible for the production of which second-messenger molecule? a. Cyclic AMP b. Calcium c. IP 3 d. Calmodulin Cyclic AMP A. Answer a is correct. Adenylyl cyclase is the enzyme that produces camp when activated by a G protein. B. Answer b is incorrect. Calcium is an important second messenger; however, it is not the product of an enzyme. C. Answer c is incorrect. IP 3 is an important second-messenger molecule; however, it is produced when the enzyme phospholipase C is activated by a G protein.

6 D. Answer d is incorrect. Calmodulin is involved in mediating the influence of the calcium in the cell. 12. The response to signaling through G protein-coupled receptors can vary in different cells because a. all receptors act through the same G protein b. different isoforms of a receptor bind the same ligand but activate different effectors c. the amount of receptors in the membrane differs in different cell types d. different receptors can activate the same effector A. Answer a is incorrect. All receptors do not activate the same G protein. There are a limited number of G proteins, but not a single G protein for all receptors. different isoforms of a receptor bind the same ligand but activate different effectors A. Answer b is correct. A single receptor type can have different isoforms in different cells that bind the same ligand but activate different signaling pathways. A. Answer c is incorrect. The number of receptors in the membrane does not determine specificity of signaling. A. Answer d is incorrect. This would produce the opposite effect; that is, two different signals producing the same response, not the same signal producing a different response. 13. What is the function of the tight junctions in the formation of a tissue? a. Tight junctions connect one cell to the next, creating a barrier between the cells. b. Tight junctions form a strong anchor between two cells. c. Tight junctions allow for the movement of small molecules between cells. d. Tight junctions connect the cell to the extracellular matrix. Tight junctions connect one cell to the next, creating a barrier between the cells. A. Answer a is correct. A tight junction creates a seal between two cells that prevents the movement of molecules between them. B. Answer b is incorrect. Tight junctions are formed between cells; however, they are not involved in anchoring the cell. Desmosomes act as anchors between cells. C. Answer c is incorrect. Gap junctions form tunnels that connect the cytoplasm of two neighboring cells.

7 D. Answer d is incorrect. Anchoring junctions form connections between the extracellular matrix and the cell s cytoskeleton. 14. Cadherins and intermediate filament proteins are associated with, whereas connexons are associated with a. tight junctions; anchoring junctions b. cell surface markers; tight junctions c. desmosomes; gap junctions d. adherens junctions; plasmodesmata A. Answer a is incorrect. Tight junction proteins are associated with tight junctions while integrins are associated with the anchoring junctions. B. Answer b is incorrect. Cell-surface markers are associated with recognition of self. Connexons are not part of tight junctions. desmosomes; gap junctions C. Answer c is correct. Desmosomes are formed by the binding between cadherin proteins on the surface of the cell and stabilized by intermediate filament proteins in the cytoplasm. Gap junctions are formed by connexon proteins embedded in the cell s plasma membrane. D. Answer d is incorrect. Adherens junctions are formed by the interaction of integrin proteins and the extracellular matrix. Plasmodesmata are extensions of plasma membrane that connect the cytoplasm of multiple plant cells through openings in the cell wall. 15. Cells are able to anchor themselves to the extracellular matrix through the activity of a. connexon proteins b. MHC proteins c. cadherin proteins d. integrin proteins A. Answer a is incorrect. Connexon proteins are involved in the formation of gap junctions. B. Answer b is incorrect. The MHC proteins are involved in the immune system s ability to distinguish self from nonself. C. Answer c is incorrect. Cadherin proteins participate in the formation of desmosomes that anchor cells together. integrin proteins D. Answer d is correct. Integrin proteins bind to the extracellular matrix outside a cell and to the cell s cytoskeleton within the cytoplasm.

8 Challenge Questions 1. Describe the common features found in all examples of cellular signaling discussed in this chapter. Provide examples to illustrate your answer. Answer All signaling events start with a ligand binding to a receptor. The receptor initiates a chain of events that ultimately leads to a change in cellular behavior. In some cases the change is immediate such as when ligand binding results in the opening of a channel. In other cases the change requires more time before it occurs such as when the MAP kinase pathway becomes activated and multiple different kinases become activated and deactivated or when G proteins interact with effector proteins, leading to the production of second messengers. Some signals only affect a cell for a short time (such as the channel example), but other signals can permanently change the cell by changing gene expression, and therefore the number and kind of proteins found in the cytoplasm of the cell. 2. The sheet of cells that form the gut epithelium folds into peaks called villi and valleys called crypts. The cells within the crypt region secrete a protein, Netrin-1, that becomes concentrated within the crypts. Netrin-1 is the ligand for a receptor protein that is found on the surface of all gut epithelial cells. Netrin-1 binding triggers a signal pathway that promotes cell growth. Gut epithelial cells undergo apoptosis (cell death) in the absence of Netrin-1 ligand binding. a. How would you characterize the type of signaling (autocrine, paracrine, endocrine) found in this system? b. Predict where the greatest amount of cell growth and cell death would occur in the epithelium. c. The loss of the Netrin-1 receptor is associated with some types of colon cancer. Suggest an explanation for the link between this signaling pathway and tumor formation. Answer a. This system involves both autocrine and paracrine signaling because Netrin-1 can influence the cells within the crypt that are responsible for its production and the neighboring cells. b. The binding of Netrtin-1 to its receptor produces the signal for cell growth. This signal would be strongest in the regions of the tissue with the greatest amount of Netrin-1 that is, in the crypts. A concentration gradient of Netrin-1 exists such that the levels of this ligand are lowest at the tips of the villi. Consequently, the greatest amount of cell death would occur at the villi tips. c. Tumors occur when cell growth goes on unregulated. In the absence of Netrin-1, the Netrin-1 receptor can trigger cell death controlling the number of cells that make up the epithelial tissue. Without this mechanism for controlling cell number, tumor formation is more likely.

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