Chapter 9

1. The protein Sonic Hedgehog (SHH) plays a role in specifying the identity of digits (such as fingers and toes) in mammals. Several digits arise directly from cells that both express and respond to secreted SHH. What type of signaling would this be considered?

A. Direct contact
B. Paracrine
C. Endocrine
D. Synaptic
E. Autocrine

2. One cell sends second messengers to another cell through gap junctions. What type of signaling would this be considered?
A. Direct contact
B. Paracrine
C. Endocrine
D. Synaptic
E. Autocrine

3. In synaptic signaling, neurotransmitters are released into a space that is referred to as a:

A. chemical synapse.
B. neuron junction.
C. paracrine space.
D. gap junction.
E. plasmodesmata.

4. In response to injury, cell fragments called platelets get activated to induce clotting. Activated platelets release factors that can in turn bind to specific membrane receptors on nearby cells. What type of signaling would this be considered?
A. Direct contact
B. Paracrine
C. Endocrine
D. Synaptic
E. Autocrine

5. A researcher is working to generate a new cancer drug. Thus far, he has identified a compound that can reduce the size of tumors in the lung. However, in order for the drug to work, the lung tumor has to be small. In addition, the tumor cannot have metastasized (spread to other areas of the body). Furthermore, he knows that the drug acts to prohibit the signaling from one tumor cell to another tumor cell. Given the above information, this new drug prohibits:
A. synaptic signaling between tumor cells.
B. autocrine signaling between tumor cells.
C. paracrine signaling between tumor cells.
D. endocrine signaling between tumor cells.

6. Using a specific chemical, a cell biologist has blocked one type of channel-linked receptor in a lab rat's liver tissue. What was the likely mechanism of the chemical she used?
A. The chemical prohibits binding of a ligand to the receptor.
B. The chemical prohibits ions from entering the cell via active transport.
C. The chemical causes ions to move in the opposite direction of the ion gradient.
D. The chemical prohibits second messenger signaling.

7. Leptin is a circulating hormone that is produced by fat cells and plays a role in body metabolism and obesity. It normally binds to receptors in the brain and inhibits appetite. Studies have demonstrated that when obese mice that are leptin deficient are injected with leptin they quickly lose their excess weight. Interestingly, however, many overweight people have high levels of leptin in their bloodstream. Why do you think that the high levels of leptin in obese individuals are insufficient to curb their appetite?

A. Paracrine signaling may be disrupted in obese people with high levels of leptin.
B. Obese people who have high levels of leptin may have a leptin receptor with decreased sensitivity.
C. The form of leptin released by obese people may lack protein kinase activity.
D. In obese people with high levels of leptin, the leptin is a non-functional second messenger.

8. Vasopressin is a hormone that is primarily released when the body is low on water. Release of vasopressin causes the kidneys to conserve water by concentrating urine and decreasing urine output. However, vasopressin also has additional functions in other tissues such as the brain and blood vessels, which are not directly involved in urine production. How could it be possible for vasopressin to trigger different responses in different tissues?
A. Vasopressin can bind to, and act on, different receptor subtypes, leading to different cellular responses in different tissues.
B. Vasopressin can be released at different times to result in different effects.
C. Vasopressin binds to the same exact receptor in different tissues, but causes a different conformational change to the receptor in each tissue.
D. The kidneys have a receptor for vasopressin, but cells in the brain and blood vessels do not have a receptor for vasopressin.

9. Addison's disease is a disorder that results from a reduction in production of glucocorticoids and mineralocorticoids. Individuals with Addison's disease suffer from a variety of systemic symptoms including: muscle weakness, fever, issues with the gastrointestinal tract, and increased tanning. Considering this information, what type of signaling do you think that glucocorticoids and mineralocorticoids stimulate?
A. Direct contact
B. Paracrine
C. Endocrine
D. Synaptic
E. Autocrine

10. What is the function of a protein kinase?
A. To remove phosphate groups from proteins
B. To cleave membrane phospholipids
C. To phosphorylate GDP to generate GTP
D. To add phosphate groups onto proteins

11. You have identified a novel cytoplasmic protein. Through sequence analysis you are able to identify the presence of a number of serine/threonine phosphorylation motifs. Based on these data, you hypothesize that this protein may be a substrate for what kind of enzyme?
A. A protein kinase
B. A receptor tyrosine kinase
C. A G protein-coupled receptor
D. A tyrosine phosphatase
E. A phospholipase

12. You have identified a molecule, molecule X, that can bind to the ATP binding site of a specific protein kinase, and prevent ATP binding. You are conducting a kinase assay using this protein kinase and a known substrate of this kinase, and have set up the reaction using the proper conditions and co-factors to allow for optimal protein kinase activity. If you add molecule X to the reaction, what do you predict will be the outcome?
A. The substrate will be phosphorylated normally in the presence of molecule X.
B. Less phosphorylation of the substrate will be seen in the presence of molecule X.
C. More phosphorylation of the substrate will be seen in the presence of molecule X.

13. Why are phosphorylation and dephosphorylation reactions commonly used to regulate signal transduction pathways?
A. Phosphate groups are efficient second messengers
B. Protein kinases and phosphatases are abundant in most cells
C. The hydrolysis of bound GTP generates GDP, which can change the activity of proteins bound to GDP
D. The addition or removal of a phosphate group can expose or hide potential binding sites in proteins or change protein activity

14. You are performing an experiment to assay phosphorylation of a substrate by a protein kinase. Based on the data in the table below, what do these experimental results suggest?

A. GTP is not required for phosphorylation.
B. The substrate can undergo autophosphorylation.
C. The substrate is not required for phosphorylation.
D. The protein kinase is required for phosphorylation.

15. These molecules can directly convert extracellular signals into intracellular signals.
A. Second messengers
B. Scaffolds
C. Membrane receptors
D. Adapter proteins
E. G proteins

16. When bound to ligand, this type of receptor changes conformation to allow ions to move down their concentration gradient across the membrane:
A. Channel-linked receptor
B. Enzymatic receptor
C. G protein-coupled receptor
D. Steroid hormone receptor

17. Growth of new blood vessels is stimulated by vascular endothelial growth factor (VEGF). This ligand binds to the VEGF receptor, which leads to the dimerization and autophosphorylation of this receptor on cytoplasmic tyrosines. What type of receptor is the VEGF receptor?
A. Channel-linked receptor
B. Enzymatic receptor
C. G protein-coupled receptor
D. Steroid hormone receptor

18. What type of receptor is not an enzyme, but is directly associated with an enzyme that can hydrolyze GTP?
A. Channel-linked receptor
B. Enzymatic receptor
C. G protein-coupled receptor
D. Steroid hormone receptor

19. You are planning to perform some protein-protein interaction studies to identify a receptor for a steroid hormone you have been working on. You start by fractionating the cell. What cell fraction would you want to work with to identify the steroid hormone receptor of interest?
A. The plasma membrane fraction
B. The extracellular fraction
C. The cytoplasmic fraction
D. The mitochondrial fraction
E. The ribosomal fraction

20. What property defines most ligands for intracellular receptors?
A. They are lipid-soluble
B. They are hydrophilic
C. They are molecules that can perform significant hydrogen bonding interactions with water
D. They are large molecules

21. You are interested in developing an inhibitor for the estrogen receptor. You have identified a molecule that is small and hydrophilic. In a test tube, this inhibitor binds tightly to the estrogen receptor, and inhibits the interaction of the receptor with estrogen. Do you think that this molecule will be an effective inhibitor of the estrogen receptor in cells?
A. Yes, because it can prevent estrogen binding.
B. Yes, because it is small.
C. No, because it is hydrophilic.
D. No, because it will need to bind to the DNA-binding domain to act as an inhibitor.

22. Tamoxifen is a drug that is used to treat breast cancer. It inhibits the activities of the estrogen receptor in breast epithelial cells, which are the cells that are relevant to breast cancer. One of the concerns that scientists had during the development of Tamoxifen as a therapy for breast cancer was that other cell types require estrogen signaling for their function. For example, it is known that cells in bone tissue require estrogen signaling. As a result, there was a concern that use of Tamoxifen would lead to bone loss in patients. In reality, however, researchers were surprised to find that Tamoxifen actually led to an increase in bone density in breast cancer patients. At the same time, Tamoxifen did inhibit the activity of the estrogen receptor in breast epithelial cells in these patients. What is the best explanation for this finding?
A. Tamoxifen binds different parts of the estrogen receptor in different tissues.
B. The estrogen receptor is bound to different coactivators in different tissues.
C. Tamoxifen can only enter certain cell types.
D. Bone cells make use of a different type of estrogen receptor that does not bind to Tamoxifen.

23. A mutation in the DNA-binding domain of a steroid hormone receptor is most likely to affect what aspect of receptor function?
A. The conformational change of the receptor
B. The binding of the hormone to the receptor
C. The translocation of the receptor to the nucleus
D. The cellular response to the hormone

24. You are having lunch with an elderly friend when suddenly he begins to experience chest pain and tightness. He reaches into his pocket, gets out one of his nitroglycerin tablets and quickly takes it. After the episode passes, your friend asks you how the nitroglycerin helps his angina. You explain that nitroglycerin gets converted by cells to nitric oxide (NO) causing the smooth muscle cells of the blood vessel to relax and increase blood flow to the heart. He pushes you for a more detailed explanation, so you explain further that:
A. NO activates guanylyl cyclase, which catalyzes the synthesis of cGMP, which acts as an intracellular messenger in a pathway leading to smooth muscle relaxation.
B. NO activates a protein kinase which catalyzes the synthesis of cGMP, which acts as an intracellular messenger in a pathway leading to smooth muscle relaxation.
C. NO inhibits guanylyl cyclase, which allows the build up of cGMP, which acts as an intracellular messenger in a pathway leading to smooth muscle relaxation.
D. NO activates cGMP, which catalyzes the synthesis of guanylyl cyclase, which acts as an intracellular messenger in a pathway leading to smooth muscle relaxation.

25. What is the mechanism by which binding of testosterone to the testosterone receptor leads to upregulated gene transcription?
A. Binding of testosterone to the testosterone receptor leads to the increase in second messengers that activate a kinase cascade, ultimately leading to the activation of transcription factors that promote gene transcription.
B. Binding of testosterone to the testosterone receptor leads to the activation of a G protein that stimulates the activation of enzymes that promote gene transcription.
C. Binding of testosterone to the testosterone receptor leads to a conformational change that allows the receptor to enter the nucleus where it can bind to DNA and promote gene transcription.
D. Binding of testosterone to the testosterone receptor leads to the opening of an ion channel that leads to an increase in calcium in the cytoplasm. The increased calcium levels activate calmodulin, which can go on to activate other proteins that promote gene transcription.

26. How are receptor tyrosine kinases and steroid hormone receptors similar?
A. Both are activated by autophosphorylation
B. Both are transmembrane proteins with a single transmembrane domain
C. Both have a DNA-binding domain
D. Both have a site for binding ligand

27. Some cancers are caused by the overexpression of receptor tyrosine kinases (RTKs). It is known that RTK signaling pathways commonly stimulate cell division. Why would the overexpression of receptor tyrosine kinases lead to cancer development?
A. RTKs are activated by dimerization, caused by ligand binding. If there are too many receptors on the cell surface, it is possible that these receptors dimerize in the absence of ligand binding, thus stimulating cell division at inappropriate times.
B. If there are too many RTKs on the cell surface, this will tend to allow cells to adhere to each other. Once they adhere, RTKs from one cell can bind to RTKs from another cell, and they can activate each other leading to activation of downstream signaling pathways in both cells.
C. If there are too many RTKs on the cell surface, it is less likely that inhibitors will bind to all of the available RTKs and block their ability to enter the nucleus. As a result, some of the RTKs will be able to enter the nucleus to stimulate transcription.
D. If there are too many RTKs on the cell surface, this will promote the inhibition of autophosphorylation. In the absence of autophosphorylation, it is more likely that the RTK downstream signaling pathway will be active.

28. What signaling pathway commonly makes use of a G protein to transduce the signal?
A. Channel-linked receptor pathways
B. Steroid hormone receptor pathways
C. Receptor tyrosine kinase pathways

29. Your research project involves the characterization of a particular signal transduction pathway. Specifically, you have been studying a receptor tyrosine kinase and protein X, which initiates downstream events. You are certain that protein X is part of the signal transduction pathway, but have been unable to identify a direct protein-protein interaction between the receptor tyrosine kinase and the protein X. What should you do next in your attempt to identify a link between the receptor tyrosine kinase and protein X?
A. Try to identify a coactivator protein.
B. Try to identify proteins that act downstream of protein X.
C. Try to identify an adapter protein that can interact with both the receptor and protein X.
D. Confirm the interaction between the receptor tyrosine kinase and its ligand.

30. The protein SOS is a guanine nucleotide exchange factor for Ras. SOS helps facilitate the exchange of GDP for GTP. What would be the effect of a mutation that inhibits the interaction between SOS and Ras?
A. GTP would remain bound to Ras, thereby keeping Ras constitutively active.
B. GDP would remain bound to Ras, thereby preventing Ras activation.
C. Ras would be more likely to hydrolyze GTP to GDP.
D. There would be no effect.

31. Many receptor tyrosine kinase (RTK) pathways lead to the activation of Ras. To activate Ras, it is necessary to recruit a guanine nucleotide exchange factor to the plasma membrane, because Ras is a membrane associated protein. Guanine nucleotide exchange factors, such as SOS, stimulate the exchange of GDP for GTP. However, SOS cannot bind directly to most RTKs. The protein Grb2 has a domain that can bind to phosphorylated tyrosines, and another domain that can bind to SOS. Therefore, Grb2 can bind to active RTKs and recruit SOS to the plasma membrane. Grb2 is an example of what kind of signaling molecule?
A. Scaffold
B. Adapter protein
C. Second messenger
D. Enzyme

32. Ste5 binds to MAPKKK, MAPKK, and MAPK to organize the kinase cascade. What type of signaling molecule is Ste5?
A. Scaffold
B. Adapter protein
C. Second messenger
D. Enzyme

33. Many receptor tyrosine kinase pathways have MAPK as a downstream signaling component. MAPK can phosphorylate target proteins. What type of signaling molecule is MAPK?
A. Scaffold
B. Adapter protein
C. Second messenger
D. Enzyme

34. A small number of cell surface receptors can ultimately generate a large intracellular response due to activation of kinase cascades. This is referred to as:
A. signal amplification.
B. signal transduction.
C. signal dampening.
D. signal activation.

35. What enzyme phosphorylates MAP kinase kinase?
A. MAP kinase
B. MAP kinase kinase
C. MAP kinase kinase kinase
D. MAP phosphatase

36. The cell surface receptors that can act only indirectly on plasma membrane-bound enzymes or ion channels are called:
A. G protein-coupled receptors.
B. gated ion channels.
C. enzymatic receptors.
D. second messenger receptors.

37. G protein-coupled receptors are the largest family of cell surface receptors. Each receptor passes through the plasma membrane how many times?
A. Once
B. Three times
C. Five times
D. Seven times

38. In the nitric oxide signaling pathway, nitric oxide activates an enzyme that can convert many molecules of GTP into molecules of cGMP. cGMP is a small molecule that can diffuse through the cytoplasm and bind to an enzyme called protein kinase G (PKG). Binding of cGMP to PKG leads to a change in the confirmation of PKG that leads to its activation. What type of signaling molecule is cGMP?
A. Scaffold
B. Adapter protein
C. Second messenger
D. Enzyme

39. Some enzymatic receptors and most G protein-coupled receptors transmit the signal into the cytoplasm by utilizing other substances within the cytoplasm that are referred to as:
A. genes.
B. intracellular receptors.
C. second messengers.
D. first messengers.

40. A mutation that affects Ca++ binding to calmodulin is most likely to interfere with what aspect of a signal transduction pathway?
A. The flow of Ca++ ions through ion channel receptors
B. The cellular response to the second messenger
C. The MAP kinase cascade
D. G protein activity

41. If the effector protein phospholipase C failed to cleave phosphatidylinositol-4,5-bisphosphate (PIP2), the action of what enzyme would be affected?
A. cAMP
B. IP3
C. protein kinase A (PKA)
D. protein kinase C (PKC)

42. What is similar about G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs)?
A. Both are directly bound to G proteins
B. Both can activate phospholipase C
C. Both are enzymes
D. Both are activated by autophosphorylation

43. The function of adenylyl cyclase is to:
A. catalyze the conversion of ATP to cAMP.
B. cleave PIP2 into DAG and IP3.
C. directly activate protein kinase A (PKA).
D. stimulate the release of calcium from the endoplasmic reticulum.

44. What is the difference between Ras and the G proteins bound to G protein coupled receptors (GPCRs)?
A. Ras is an enzyme and the G proteins bound to GPCRs are not enzymes.
B. Ras is a second messenger and the G proteins bound to GPCRs are not second messengers.
C. Ras is a small G protein and the G proteins bound to GPCRs are not small G proteins.
D. Ras can activate different effector molecules and the G proteins bound to GPCRs cannot activate different effector molecules.

45. What second messenger is directly involved in activating protein kinase C (PKC)?
A. DAG
B. cAMP
C. cGMP
D. Phospholipase C
E. G protein