Hanover College



LESSON - 18 and 19

EUKARYOTIC CELL

CELL-TO-CELL SIGNALLING.

A. Objectives

- Define the different types of cell signaling: direct contact, paracrine signaling, endocrine signaling, and synaptic signaling.

- Describe and give examples of cell signaling using intracellular and extracellular receptors. What reaction is catalyzed by the adenylyl cylase? guanylyl cyclase? What is the structure of cAMP? CGMP? What is No? Give the basic structure of steroids? How do steroid hormones function?

- Signaling transduction involves signal molecules, cell surface receptors, intracellular messengers, a protein kinase cascade, and transcription factors. Explain. Explain the function of chemically gated ion channel receptors, receptor tyrosirie kinases, and G— protein—linked receptors. Give an overview of the beta—adrenergic receptor.

- List various molecules that function as intracellular secondary messengers. Give the basic structure of cAMP and inositol triphosphate. Explain the origin of both messengers. What is the source of intracellular calcium? What is the role of calmodulin?

- What are protein kinases? Identify the amino acids to which phosphates are linked. Explain how a protein kinase cascade amplifies a signal. What is the role of phosphatases?

B. Lecture outline

1. TYPES OF CELL-TO-CELL SIGNALING.

Read: Sending signals (SBM p136-137)

2. LIPOPHYLIC SIGNALS USE INTRACELLULAR RECEPTORS.

Read: Intracellular receptors (SBM p138 Figure 6-4)

3. HYDROPHYLIC SIGNALS USE CELL SURFACE RECEPTORS.

Read: Reception (SBM p137-140)

Signal transduction (SBM p140-145)

Responses to signals (SBM p145-147)

a. Different types of cell surface receptor: gated ion channels, receptor tyrosine kinase, and G protein—linked receptors.

b. Intracellular, second messengers: cAMP, calcium, and inositol triphosphate.

c. Protein kinase cascade.

C. Study Questions.

1. A Protein, located on or within a cell, that has a three dimensional shape complementary to that of a specific signal molecule is a

A. coupled channel.

B. receptor.

C. ligand.

D. hormone.

E. desmosome.

2. What is the role of cell-cell communication in eukarytoic organisms?

A. Determine the position of individual cells in the body.

B. Adjust cellular metabolism.

C. Allow individual cells to grow.

D. Controls dl division.

E. All of the above.

3. What is the activity of a signal molecule when approaching a target cell.

A. Recognize the protein receptor with the correct 3-D shape.

B. Bind to the receptor with complementary shape.

C. Induce a conformational change in the receptor molecule.

D. Change cellular activity after receptor binding.

E. All of the above.

4. Communication between cells can occur by all of the following basic mechanisms except:

A. direct contact signals.

B. digestion of the plasma membrane.

C. paracrine signals.

D. enocrine signals.

E. synaptic signals.

5. Direct contact signaling may use A. gap junctions.

B. desmosomes.

C. lipophylic ligands.

D. neurotransmitters.

E. hormones.

6. Communication that does not involve soluble, extracellular mediators A. direct contact signaling.

B. paracrine signaling.

C. synaptic signaling.

D. endocrine signaling.

E. hormonal signaling.

7. Communication using short—lived, soluble mediators is called.

A. direct contact signaling.

B. paracrine signaling.

C. synaptic signaling.

D. endocrine signaling.

E. hormonal signaling.

8. Communication of neighboring cells using labile ligands is

A. direct contact signaling.

B. paracrine signaling.

C. synaptic signaling.

D. endocrine signaling.

E. hormonal signaling.

9. Communication based on release of neurotransmitters is

A. direct contact signaling.

B. paracrine signaling.

C. synaptic signaling.

D. endocrine signaling.

E. hormonal signaling.

10. Communication using stable molecules distributed widely throughout the body is called

A. direct contact signaling.

B. paracrine signaling.

C. synaptic signaling.

D. endocrine signaling.

E. autocrine signaling.

11. Corticosteroids, sex hormones, vitamin D and thyroxine bind to

A. G proteins

B. cell surface receptors.

C. intracellular receptors.

D. DNA.

E. cAMP.

12. The intracellular target f or NO in the smooth muscles of small blood vessels is

A. phospholipase C.

B. receptor tyrosine kinase.

C. adenylyl cyclase.

D. guanyJ.yl cyclase.

E. G protein.

13. production of NO by endothelial cells causes the muscle cells of the blood vessel wall to

A. relax.

B. contract.

C. divide.

D. die.

E. secrete.

14. The molecules that convert extracellular signals into

intracellular ones are

A. neurotransmitters.

B. peptide hormones.

C. cell surface receptors.

D. transcription facotrs.

E. cadherins.

15. The properties of a gated channel are

A. peptide chain that winds repeatedly across the membrane.

B. the presence of a pore in the center of the protein.

C. the pore connects the extracellular fluid with the

cytoplasm.

D. the pore is big enough for ions to pass through.

E. all, of the above.

16. Water—soluble ligands signal cells by using

A. major histocompatibility molecules.

B. coupled transport.

C. hemidesmosomes.

D. cell surface receptors.

E. intracellular receptors.

17. Receptor tyrosin kinases A. have enzyme activity. B. are single—pass transmembrane

proteins.

C. bind the signal molecule with the extracellu].ar domain.

D. have a cytopl.asmic domain that is a tyrosine kinase.

E. all of the above.

18. When a ligand binds to a receptor tyrosine kinase

A. phosphate is removed from proteins.

B. phosphate is added to tyrosine residues of proteins.

C. phosphate is added to serine and threonine residues of proteins.

D. phosphol.ipids are hydrol.ysed. E. cAMP is produced.

19. When a ligand binds to a G protein-linked receptor, membrane—associated enzymes are activated by

A. G protein.

B. protein phosphorylation.

C. protein dephosphorylation.

D. inositol triphosphate.

E. cAMP.

20. A G-protein is a

A. very small protein.

B. an extracellular ligand.

C. a GTP/GDP binding protein.

D. glycoprotein.

E. guanylyl cyclase.

21. The beta—adrenergic receptor is an example of a

A. receptor tyrose kinase.

B. gated ion channel.

C. G protein.

D. g protein-linked receptor.

E. adenylyl cyclase.

22. cAMP is synthesized by

A. adenylyl cyclase

B. guanylyl cyclase.

C. tyrosine kinase.

D. A-kinase.

E. phosphatase.

23. cAMP is synthesized by hydrolysis of

A. GTP.

B. ATP.

C. tyrosine phosphatase.

D. phospholipid

E. inositol triphosphate.

24. Second messengers of the cell include

A. cAMP.

B. Ca++

C. inositol triphosphate (1P3).

D. diacyl glycerol (DAG).

E. all of the above.

25. Which are examples of second messengers?

A. sodium and potassium ions.

B. amino acids and proteins.

C. steroids and triglycerides.

D. vitamin D and E.

E. cAMP, Ca++, and inositol triphosphate and diacy].

glycerol.

26. The concentration of calcium ions inside the cytoplasm is about

A. 10-3 M

B. 10-4 M.

C. 10-5 M.

D. 10-6 M.

E. 10-7 M.

27. The concentration of calcium ions outside the cell is about

A. 10-3 M

B. 10-4 M.

C. 10-5 M.

D. 10-6 M.

E. 10-7 M.

28. The intracellular storage site of calcium ions is the

A. Golgi complex.

B. lysosomal network.

C. endoplasmic reticulum.

D. mitochondrial matrix.

E. nycJ.ear envelope.

29. Phospholipases hydrolyse

A. proteins.

B. carbohydrates.

C. nucleic acids.

D. phospholipids.

E. GTP.

30. Phopholipase C cleaves phosphatidyl inosito].-biphosphate in

A. two secon messengers.

B. cAMP.

C. G protein.

D. protein kinases.

E. protein kinase cascade.

31. Phospholipase C cleaves phosphatidyl inositol-biphosphate in

A. diacyJ. glycerol (DAG).

B. inositol triphosphate (1P3).

C. cAMP.

D. Ca-almodulin.

E. DAG and P13.

32. The water-soluble second messenger generated by phospholipase C is

A. diacyl glycerol (DAG).

B. inositol triphosphate (1P3).

C. cAMP.

D. Ca-almodulin.

E. DAG and P13.

33. The lipid-soluble second messenger generated by phospholipase C is

A. diacyl glycerol (DAG).

B. inositol triphosphate (1P3).

C. cAMP.

D. Ca—almodulin.

E. DAG and P13.

34. Intracellular calcium ions exert many of their functions by binding to

A. actin filaments.

B. integrin.

C. calmodulin.

D. cAMP.

E. diacyl glycerol.

35. Which of the following statements is not true? During signal transduction

A. the cell converts an extracellular signal into an intracellular signal

B. nitric oxide is typically produced

C. the signal is amplified

D. relay of the signal is regulated

E. the signal is terminated

36. Which of the following statements is not true? Local regulators

A. are signaling molecules

B. typically carry on paracrine regulation

C. include growth factors

D. transmit electrical signals

E. signal target cells

37. In animals, hormones

A. are secreted by endocrine glands

B. are electrical signals

C. include neurotransmitters

D. terminate signals during signal transduction

E. are primarily produced by glands with ducts

38. When a ligand binds with a receptor,

A. G proteins are inactivated

B. a third messenger is activated

C. cell signaling is stopped

D. the signaling cell is activated

E. the receptor is activated

39. A G protein-linked receptor

A. inactivates G proteins

B. activates first messengers

C. consists of 18 transmembrane alpha helices

D. is a member of a family of about 10 different receptors

E. has a tail that extends into the cytosol and has a binding site for a G protein

40. An enzyme-linked receptor

A. is an integral membrane protein

B. would not be found on plant cell surfaces

C. aggregates with another enzyme-linked receptor when a ligand binds to it

` D. is typically an adenylyl cyclase molecule

E. typically activates ion channels

41. G proteins

A. relay a message from the activated receptor to an enzyme that activates a second messenger

B. are GTP molecules

C. terminate cell signaling

D. directly activate protein kinases

E. function as first messengers

42. When activated, a G protein

A. consists of four subunits

B. releases GDP and binds with GTP

C. detaches from adenylyl cyclase

D. acts as a second messenger

E. typically terminates a signaling cascade

43. Which is the correct sequence?

1. protein kinase activated 2. adenylyl cyclase activated 3. cAMP produced 4. proteins phosphorylated

5. G protein activated

A. 1, 2, 3, 5, 4

B. 5, 3, 2, 1, 4

C. 5, 2, 3, 4, 1

D. 5, 2, 3, 1, 4

E. 2, 3, 1, 4, 5

44. Which is the correct sequence?

1. phospholipase activated 2. G protein activated 3. PIP2 split 4. proteins phosphorylated 5. DAG produced

A. 1, 2, 5, 3, 4,

B. 4, 2, 3, 1, 5

C. 2, 1, 3, 5, 4

D. 5, 2, 3, 1, 4

E. 2, 3, 5, 4, 1

45. Calcium ions

A. act as second messengers

B. split calmodulin

C. are kept at higher concentration in the cytosol than in the extracellular fluid

D. are produced in the ER by protein kinases and protein phosphatases

E. typically terminate signaling cascades

46. Ras proteins

A. act as second messengers

B. are growth factors

C. are transcription factors

D. are a group of small R proteins

E. trigger a cascade of reactions that can activate genes

47. Nitric oxide

A. binds directly with GTP

B. stimulates the blood vessel dilation necessary for penile erection

C. is released by many target cells

D. acts as a second messenger

E. is a signaling molecule that combines with enzyme-linked receptors

48. Scaffolding proteins

A. release kinases and phosphatases into the extracellular fluid

B. increase the probability that an enzyme can be used by several different pathways

C. increase accuracy but slow signaling cascades

D. organize groups of intracellular signaling molecules into signaling complexes

E. are found mainly in plant cells

49. Each adenylyl cyclase molecule produces many cAMP molecules. This is an example of

A. receptor up-regulation

B. receptor down-regulation

C. signal amplification

D. scaffolding

E. paracrine regulation

1. Quorum sensing would most likely occur when:

A. Dictyostelium senses cyclic AMP.

B. tobacco plants are attacked by insects.

C. bacteria reach a certain critical concentration.

D. predator insects eat herbivorous insects.

E. insulin binds to target cells.

1. Which of the following lists the correct sequence of events involved in cell signaling?

A. amplifying, signal transducing, receiving, responding

B. signal transducing, sending, receiving, terminating

C. sending, signal transducing, receiving, amplifying

D. receiving, sending, signal transducing, responding

E. sending, receiving, signal transducing, responding

2. Paracrine signaling is different from other types of signaling in that the signaling molecule:

A. is produced by endocrine glands.

B. binds to a receptor.

C. is secreted by neurons.

D. is transported in the blood.

E. acts on nearby cells.

3. Which of the following is stored in cells of the immune system and released during an allergic reaction?

A. nitric oxide

B. a growth factor

C. histamine

D. a prostaglandin

E. a neurotransmitter

4. Which of the following is released by cells lining blood vessels and causes an increase in blood pressure?

A. histamine

B. acetylcholine

C. cyclic AMP

D. nitric oxide

E. prostaglandin

5. Which of the following would most likely diffuse across a synapse?

A. insulin

B. NO

C. histamine

D. acetylcholine

E. prostaglandins

6. In classical endocrine signaling, hormones are transported to target cells:

A. across a synapse.

B. in the blood.

C. in interstitial fluid.

D. via direct contact.

E. through the air.

7. Which of the following statements concerning receptors is FALSE?

A. They are found inside the cell and on the cell surface.

B. They are proteins or glycoproteins.

C. They are also called ligands.

D. They are highly selective.

E. They are activated by binding to a signaling molecule.

8. A receptor on the cell surface usually has several domains. The function of the external domain is:

A. transmitting the signal to the inside of the cell.

B. holding the receptor within the membrane.

C. attaching the receptor to the DNA.

D. functioning as an enzyme.

E. binding the signaling molecule.

9. A receptor in plant cells that responds to red light is:

A. brassinolide.

B. diacylglycerol.

C. rhodopsin.

D. cryptochrome.

E. phytochrome.

10. Under which of the following situations would receptor down-regulation most likely occur?

A. The concentration of a neurotransmitter is too low.

B. The concentration of a hormone is too high.

C. The number of receptors in the plasma membrane is too low.

D. The number of G proteins is too high.

E. The cell is unable to manufacture cyclic AMP.

11. As a result of receptor up-regulation:

A. the number of genes that code for a receptor increases.

B. the sensitivity of a cell to a hormone decreases.

C. the number of receptors decreases.

D. the concentration of hormone molecules in the blood increases.

E. a hormone’s signal is amplified.

12. In contrast to a G protein-linked receptor and an enzyme-linked receptor, a channel-linked receptor:

A. is located on the cell surface.

B. is composed of seven alpha helices.

C. couples signaling molecules to signal transduction pathways.

D. is a ligand-gated channel.

E. functions as a tyrosine kinase.

13. When acetylcholine binds its receptor on the surface of a muscle cell, which of the following happens next?

A. G protein is activated.

B. Tyrosine kinase is activated.

C. Tyrosine is phosphorylated.

D. A neurotransmitter crosses the synapse.

E. A sodium gate opens.

14. The outer part of a G protein receptor binds ______, and its inner part binds _______.

A. the signaling molecule; tyrosine kinase

B. the signaling molecule; a G protein

C. G protein; tyrosine kinase

D. G protein; an ion channel

E. an ion channel; a G protein

15. Which of the following is NOT an example of an enzyme-linked receptor?

A. a tyrosine kinase

B. the brassinolide receptor

C. the GABA receptor

D. the ethylene receptor

E. a histidine kinase

16. An example of a signaling molecule that binds with a receptor on the cell surface is:

A. insulin.

B. ecdysone.

C. Vitamin D.

D. Vitamin A.

E. nitric oxide.

17. Which of the following statements concerning intracellular receptors is FALSE?

A. Their ligands are hydrophobic.

B. Most are transcription factors.

C. Some are located in the cytosol.

D. After binding their ligand, they move out of the cell.

E. Some are bound to DNA.

18. One difference between the ion channel-linked receptors for GABA and acetylcholine is that when GABA binds its receptor:

A. muscle contraction is inhibited.

B. sodium ions enter the cell.

C. muscle contraction is stimulated.

D. neural signaling is inhibited.

E. chloride ions rush out of the neuron.

19. An example of a neurotransmitter that opens ligand-gated sodium channels is:

A. GABA.

B. acetylcholine.

C. ecdysone.

D. NO.

E. cortisol.

20. When a receptor binds to its G protein, which of the following happens next?

A. The signaling molecule binds to the receptor.

B. The G protein activates an enzyme.

C. The three G protein subunits come together.

D. GTP is replaced by GDP.

E. GDP is replaced by GTP.

21. Which of the following statements concerning G protein is FALSE?

A. Its subunits can separate.

B. One subunit is a GTPase.

C. One subunit binds GTP.

D. One subunit binds GDP.

E. One subunit binds ATP.

22. A molecule that is a first messenger but not a second messenger is:

A. cyclic AMP.

B. G protein.

C. adenylyl cyclase.

D. protein kinase.

E. acetylcholine.

23. An example of a second messenger is:

A. protein kinase A.

B. an ion channel.

C. cyclic AMP.

D. GABA.

E. insulin.

24. Adenylyl cyclase catalyzes the reaction in which:

A. a protein is phosphorylated.

B. ATP is converted to cAMP.

C. GTP is converted to GDP.

D. PIP2 is split.

E. calcium ions bind calmodulin.

25. Adenylyl cyclase is activated directly by:

A. a G protein subunit bound to GTP.

B. a G protein subunit bound to GDP.

C. cAMP.

D. a protein kinase.

E. a hormone.

26. In the signal transduction pathway involving cAMP, once cAMP is formed, it then activates:

A. protein kinase A.

B. adenylyl cyclase.

C. G protein.

D. protein kinase C.

E. IP3.

27. A protein kinase catalyzes the reaction in which:

A. a protein loses a phosphate group.

B. a protein is phosphorylated.

C. G protein is activated.

D. ATP is converted to cAMP.

E. GTP is converted to GDP.

28. In the cAMP signal transduction pathway, once a protein kinase is activated, which of the following happens next?

A. G protein is activated.

B. Adenylyl cyclase is activated.

C. GDP is replaced by GTP.

D. cAMP is converted to ATP.

E. The protein kinase activates a cellular response.

29. Phospholipase C catalyzes the reaction in which:

A. IP3 is converted to DAG.

B. PIP2 is split.

C. a protein kinase is activated.

D. calcium ions are released from the ER.

E. DAG is converted to PIP2.

30. In the phospholipase C signal transduction pathway, which are second messengers?

A. phospholipase C and G protein

B. PIP2 and IP3

C. cAMP and IP3

D. phospholipase C and protein kinase A

E. IP3 and DAG

31. What activates protein kinase C?

A. IP3

B. DAG

C. cAMP

D. PIP2

E. calcium ions

32. In the IP3 pathway, what is the function of IP3?

A. activate protein kinase C

B. activate phospholipase C

C. phosphorylate a protein

D. bind calcium channels in the ER

E. activate adenylyl cyclase

33. Which of the following statements concerning calcium ions is FALSE?

A. They are involved in fertilization, blood clotting, and microtubule disassembly.

B. Their concentration in the cytosol rises when Ca2+ gates open in the ER.

C. Their concentration in the cytosol is usually higher than in the extracellular fluid.

D. They can act by themselves, without binding to calmodulin.

E. They can exert an effect after binding to calmodulin.

34. Calmodulin is a:

A. hormone.

B. calcium-binding protein.

C. phosphatase.

D. protein kinase.

E. phospholipase.

35. Which of the following statements concerning calmodulin is FALSE?

A. It activates protein kinases.

B. It activates phosphatases.

C. It is a protein.

D. It is found in all eukaryotic cells studied.

E. It binds a maximum of three calcium ions.

36. Most enzyme-linked receptors are:

A. phospholipases.

B. adenylyl cyclases.

C. tyrosine kinases.

D. G proteins.

E. ion channels.

37. Which of the following statements concerning Ras proteins is FALSE?

A. They are inactivated when phosphorylated.

B. They are G proteins.

C. They are active when bound to GTP.

D. They are activated by tyrosine kinase receptors.

E. They include MAP kinases.

38. The main signaling cascade for cell division and differentiation is the _______ cascade.

A. phospholipase C

B. MAP kinase

C. phosphoinositol

D. cAMP

E. calcium-calmodulin

39. You conduct an experiment in which you inactivate Ras proteins in fibroblast cells. Which of the following is the most immediate consequence of this procedure?

A. The fibroblasts synthesized excess G protein.

B. The fibroblasts synthesized excess DAG.

C. The fibroblasts no longer responded to calmodulin.

D. The fibroblases no longer synthesized DNA in response to growth factors.

E. The fibroblasts divided uncontrollably.

40. Which of the following statements concerning intracellular receptors is FALSE?

A. Some bind hydrophobic signaling molecules.

B. Some function as transcription factors.

C. They diffuse across the plasma membrane of target cells.

D. The ligand-receptor complex can activate genes.

E. The ligand-receptor complex can inactivate genes.

41. Nitric oxide binds _________ which is ________ target cells.

A. tyrosine kinase; on the surface of

B. adenylyl cyclase; on the surface of

C. guanylyl cyclase; on the surface of

D. adenylyl cyclase; inside

E. guanylyl cyclase; inside

42. The drug sildenafil (Viagra) exerts its effect by:

A. preventing the breakdown of cGMP.

B. preventing the breakdown of GTP.

C. preventing the breakdown of cAMP.

D. stimulating the synthesis of cGMP.

E. stimulating the synthesis of cAMP.

43. The function of scaffolding proteins is to:

A. phosphorylate proteins in a cascade.

B. dephosphorylate proteins in a cascade.

C. convert ATP and GTP to cAMP and cGMP, respectively.

D. regulate the MAP kinase pathway.

E. stimulate the release of calcium ions from the ER.

44. Integrins are unusual in that they:

A. are steroids.

B. are specific transmembrane proteins.

C. respond to information received from inside and outside the cell.

D. stimulate both the Ras pathway as well as the IP3 pathway.

E. are found only in Arabidopsis thaliana.

45. Which of the following responses involves the activation of ion channels?

A. Ras pathway activation of microfilament assembly in neutrophils

B. steroid hormone regulation of gene expression

C. Ras pathway activation of genes for cell division

D. peptide-stimulated assembly of microtubule assembly in neutrophils

E. serotonin-stimulated transmission of a neural impulse

46. When Arabidopsis thaliana is exposed to drought conditions, the concentration of abscisic acid concentration _______ which leads to the ________.

A. increases; opening of stomata

B. increases; closing of stomata

C. decreases; opening of stomata

D. decreases; closing of stomata

E. decreases; further dehydration of the plant

47. Phosphodiesterase catalyzes the conversion of:

A. a protein to a phosphorylated protein.

B. GDP to GTP.

C. cAMP to AMP.

D. IP3 to PIP2.

E. calcium to calcium-calmodulin.

48. All of the following are examples of signal termination EXCEPT:

A. one cAMP molecule activating many protein kinases.

B. phosphodiesterase converting cGMP to GTP.

C. GTPase converting GTP to GDP.

D. the inactivation of G protein by the cholera toxin.

E. phosphatase removing the phosphate group from a protein.

49. The cholera toxin causes a(n) _______ of chloride channels in cells of the intestine and the resulting ___________.

A. closing; loss of blood

B. closing; movement of neutrophils toward the bacterium

C. opening; assembly of microtubules

D. opening; gain of water

E. opening; loss of water

50. Choanoflagellates have been important for the study of cell communication evolution because choanoflagellates have:

A. signal transduction pathways unlike those in other bacteria.

B. signaling molecules similar to those of other protists.

C. signal transduction pathways that interfere with the cells they infect.

D. protein kinases similar to those in animals.

E. G proteins different from those in prokaryotes.

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