Deck 13: Fundamentals of Signal Transduction

Question 1

During signal transduction that involves heterotrimeric G proteins, the event that immediately precedes the dissociation to alpha monomer and beta-gamma dimer is the

A) binding of a hormone ligand to the intact heterotrimer.
B) creation of new protein-protein interactions.
C) exchange of guanine nucleotides on the alpha subunit.
D) hydrolysis of guanosine triphosphate by the beta subunit.
E) posttranslational modification of the gamma subunit with a lipid anchor.

Answer 1

exchange of guanine nucleotides on the alpha subunit.

Question 2

Which of the following is NOT an intracellular mediator (second messenger) of hormone action?

A) G protein
B) cAMP
C) calmodulin
D) diacylglycerol (DG)
E) inositol triphosphate (IP3)

Answer 2

G protein

Question 3

What is required for STAT (signal transducers and activators of transcription) to respond to a cytokine signal?

A) Binding of cytokine to intracellular receptor
B) Dissociation of the receptor subunits
C) Dissociation of the STAT subunits
D) Formation of cAMP
E) Phosphorylation of the cytokine receptor

Answer 3

Phosphorylation of the cytokine receptor

Question 4

What is the immediate trigger for the dissociation of the α and βγ subunits of the G-protein?

A) Association with adenyl cyclase
B) Binding of GTP
C) Dissociation of GDP
D) Dissociation of hormone
E) Hydrolysis of GTP

Question 5

In the hormonal activation of adenylate cyclase, and the subsequent formation of cyclic AMP, which of the following components is NOT necessary?

A) hormone receptor
B) GTP
C) ATP
D) GDP
E) guanyl nucleotide regulatory protein

Question 6

To what type of receptor do most neurotransmitters bind on the post-synaptic membrane?

A) Adenyl cyclase-associated
B) Autophosphorylating
C) Ion channel
D) PKC-associated
E) Voltage-gated channel

Question 7

What type of signaling are steroids and polypeptides involved in?

A) Autocrine
B) Endocrine
C) Juxtacrine
D) Paracrine
E) Synaptic

Question 8

Where is intracellular calcium stored that can rapidly released when needed?

A) Endoplasmic reticulum
B) Golgi
C) Lysosomes
D) Mitochondria
E) Nucleus

Question 9

Why are K_D and EC₅₀ usually not the same?

A) Not all receptors are capable of activating cell response
B) Not all receptors are capable of binding ligand
C) Some receptors are inactive
D) Some receptors bind more than one ligand
E) The cell has "spare receptors"

Question 10

Adenylyl cyclase

A) catalyzes the ADP ribosylation of proteins.
B) catalyzes the dephosphorylation of phospho?Ser residues on enzymes.
C) catalyzes the hydrolysis of ATP to ADP and Pi.
D) diffuses to the nucleus to function as a transcription factor.
E) is regulated by protein-protein interactions.

Question 11

What is cell-cell signaling that requires the cells to be in contact called?

A) Autocrine
B) Endocrine
C) Juxtacrine
D) Paracrine
E) Synaptic

Question 12

What characteristic is shared by molecules that signal via binding to intracellular receptors?

A) Acidity
B) Aliphatic structure
C) Hydrophilicity
D) Hydrophobicity
E) Peptide nature

Question 13

What type of regulation controls the activity of protein kinase A?

A) Allosteric interaction
B) Compartmentation
C) Covalent modification
D) Induction
E) Protein-protein interaction

Question 14

Plasma membrane G protein? coupled receptors share which of these characteristics?

A) catalytic activity for synthesis of a cyclic nucleoside monophosphate
B) covalent modification by ADP?ribosylation
C) identical primary sequences in the cytosolic domains
D) ligand binding site on the external surface
E) transmembrane core consisting of 10 alpha-helices.

Question 15

What molecule is the most common ligand for "gating" calcium channels?

A) ATP
B) cAMP
C) cGMP
D) Diacylglycerol
E) IP3

Question 16

What is the major type of cell that responds to cytokines?

A) Blood-forming
B) Fibroblasts
C) Hepatic
D) Peripheral nervous system
E) Smooth muscle

Question 17

Acetylcholine can work as a ligand-gated ion channel receptor in skeletal muscle. How does it work in the heart?

A) As a ligand-gated channel
B) By a juxtacrine mechanism
C) By promoting release of cytokines
D) Via a G-protein-linked receptor
E) Via an enzyme-linked receptor

Question 18

What is the most common event in the type of intracellular signal transduction that uses a second messenger?

A) Acetylation
B) Carboxylation
C) Glucuronidation
D) Phosphorylation
E) Sulfation

Question 19

As regards attenuation/control of the PI cycle second messengers, which of the following statements, if any, is/are true?

A) Diacylglycerol (DAG) can be directly converted to Phosphatidic Acid.
B) Diacylglycerol (DAG) can also be converted to a fatty acid and a monoacylglycerol.
C) Upon ligand binding, GTP is exchanged for GDP on a monomeric G protein then hydrolysis of GTP to GDP will inactivate the G protein.
D) All of the above.
E) None of the above.

Question 20

After a ligand-receptor complex enters a cell, how is the ligand disaggregated from the receptor so that the receptor can be reincorporated in the cell membrane?

A) Alteration of lysosomal pH separates the molecules
B) Both return to membrane, and ligand is degraded extracellularly
C) Covalent binding of two ligands to each other
D) Degradation of receptor and ligand in the lysosome
E) Transfer to nucleus where ligand binds DNA

Question 21

Why does endocrine signaling result in a long-term response?

A) The hormone is bound covalently to the receptor
B) The hormone is metabolized slowly
C) The receptor has a high affinity for hormone
D) There is a high concentration of hormone in blood
E) There is a rapid rate of synthesis of hormone

Question 22

Adenylate cyclase

A) depends upon GTP for activation.
B) catalyzes the formation of cyclic AMP from AMP.
C) is stimulated in fat cells by the binding of insulin.
D) is a soluble protein found in almost all eukaryotic cells.
E) is feedback regulated by ATP.

Question 23

Signal transduction through the insulin receptor is regulated by autophosphorylation of ______________ residues.

A) aspartate
B) histidine
C) serine
D) threonine
E) tyrosine

Question 24

What happens when tyrosines on receptor tyrosine kinases are autophosphorylated?

A) Additional ligand is bound
B) The ligand is degraded
C) The receptor dissociates from the membrane
D) The receptors are dimerized
E) They are recognized by other proteins

Question 25

Extracellular calcium has approximately the same concentration as the intra-organelle-stored calcium. Approximately what is this concentration?

A) 10^-1 M
B) 10^-3 M
C) 10^-6 M
D) 10^-9 M
E) 10^-12 M

Question 26

Which amino acid is modified when cholera toxin activates the G-protein cascade?

A) Arginine in the a subunit
B) Glutamate in the adenyl cyclase
C) Histidine in protein kinase A
D) Lysine in the ab complex
E) Tyrosine in the receptor

Question 27

The participation of nitric oxide in signal transduction

A) depends upon interaction with a heterotrimeric guanine nucleotide-binding protein.
B) is mediated by a receptor localized in the nucleus.
C) requires the oxidation of lysine by nitric oxide synthase.
D) results in the activation of guanylyl cyclase.

Question 28

As regards receptors coupled to Gs (G-stimulatory) and cAMP, which of the following is false?

A) Binding of ligand to its receptor activates another distinct protein which catalyzes the displacement of GDP with GTP on the alpha Gs subunit.
B) The GTP?Gs alpha subunit dissociates from the beta/gamma subunits and activates adenylate cyclase.
C) Adenylate cyclase catalyzes the conversion of ATP to cAMP.
D) cAMP activates cAMP dependent protein kinase by binding to the regulatory subunits which causes dissociation of the regulatory subunits from the catalytic subunits.
E) The catalytic subunit of cAMP dependent protein kinase can phosphorylate proteins on serine.

Question 29

Diacylglycerol is a(n)____________ that promotes _____________.

A) insulin agonist; tyrosine phosphorylation
B) phosphodiesterase inhibitor; cAMP accumulation
C) second messenger; protein kinase C activation
D) steroid-like hormone; protein dimerization

Question 30

The compound transferred to a protein by cholera toxin is

A) ADP
B) NAD⁺
C) ADPribose
D) GMP
E) NADP⁺

Question 31

Which of the following is a TRUE statement?

A) All protein kinases are activated by cyclic AMP.
B) The subunit of the protein kinase that binds cyclic AMP is the catalytic subunit.
C) Caffeine increases the rate of cyclic AMP degradation.
D) Hormones activate adenylate cyclase by binding directly to the adenylate cyclase molecule.
E) The enzyme that inactivates cyclic AMP is a phosphodiesterase.

Question 32

In skeletal muscle cells _______________ is responsible for the flux of Ca²⁺ from the cytosol to the lumen of the sarcoplasmic reticulum.

A) calmodulin-dependent protein kinase
B) Ca²⁺ - ATPase
C) nitric oxide synthase
D) phospholipase C-beta
E) protein kinase C

Question 33

Cyclic AMP can activate the synthesis of some enzymes. It is likely that the mechanism involves

A) binding of free cAMP to a nucleotide sequence in the promoter region of the gene for the enzyme.
B) phosphorylation of an acidic protein which is bound to the gene for the enzyme.
C) phosphorylation of a glucocorticoid receptor protein which then migrates to the nucleus and activates the gene for the enzyme.
D) binding of cAMP to a protein kinase regulatory subunit which migrates to the nucleus, binds to chromatin, and activates the gene for the protein.
E) phosphorylation of initiation factor IF-2 which stimulates translation of the mRNA for the enzymes.

Question 34

Autocrine regulation refers to

A) secretion of a chemical regulator which is transported to different tissues via the bloodstream where it acts to regulate cell metabolism.
B) synthesis and secretion of a hormone.
C) control of the cellular ATP levels by mitogenic agents.
D) synthesis and secretion of an autostimulatory growth regulating agent.
E) None of the above.

Question 35

There are many types of proteins and protein domains that interact with signaling molecules. What domain interacts with inositol phospholipids?

A) Phosphorylation site
B) Phosphotyrosine-binding site
C) Plekstrin homology
D) Src-homology type 2
E) Src-homology type 3

Question 36

Which phospholipase releases arachidonic acid from the membrane?

A) A1
B) A2
C) B
D) C
E) D

Question 37

What are the end products of arachidonic acid metabolism?

A) Cyclic nucleotides
B) Cytokines
C) Eicosanoids
D) Lysolecithins
E) Steroid hormones

Question 38

What type of signaling involves molecules called "local mediators"?

A) Autocrine
B) Endocrine
C) Juxtacrine
D) Paracrine
E) Synaptic

Question 39

All of the following statements are true about cyclic AMP-dependent protein kinase EXCEPT which one?

A) It is composed of a cyclic AMP binding protein dimer and 2 catalytic subunits.
B) It principally catalyzes the phosphorylation of tyrosine residues on proteins.
C) It catalyzes the conversion of inactive phosphorylase kinase to active phosphorylase kinase.
D) It activates hormone-sensitive lipase.
E) It inhibits glycogen synthase.

Question 40

Atrial natriuretic factor (ANF) stimulates guanylate cyclase in vascular smooth muscle and kidney. Where is ANF synthesized?

A) Adrenals
B) Heart
C) Intestines
D) Liver
E) Lung

Question 41

What type of modification is promoted on G-proteins by cholera toxin?

A) ADP-ribosylation
B) Deamination
C) N-acetylation
D) Phosphorylation
E) Sulfhydryl hydrolysis

Question 42

In what way do cytokine receptors differ from receptor tyrosine kinases?

A) The carboxyl end is intracellular
B) They are associated with a G-protein
C) They are made of several transmembrane helices
D) They do not span the membrane
E) They have no inherent enzyme activity

Question 43

Some calmodulin kinases, such as CAM kinase II, remain active after calcium concentration has returned to the baseline. How is this achieved?

A) Autophosphorylation
B) Calcium bind covalently to CAM
C) CAM associates with another activating ion
D) CAM binds to another protein
E) CAM is cleaved at the amino terminal

Question 44

The role of phosphorylation of protein Tyr residues during signal transduction serves to

A) deplete a pool of protein?bound Ca²⁺.
B) direct certain receptors to the endoplasmic reticulum.
C) promote specific interactions between proteins.
D) regulate the conversion of normal proteins to oncoproteins.
E) stimulate the synthesis of cyclic-AMP.

Question 45

What are ligands that bind receptor but produce no subsequent second messenger called?

A) Antagonist
B) Competitor
C) Disrupter
D) Inhibitor
E) Negator

Question 46

In the figure above which letter represents EC₅₀?

A) A
B) B
C) C
D) D

Question 47

How many of the 14 domains described for adenyl cyclase span the membrane?

A) 5
B) 7
C) 9
D) 12
E) 14

Question 48

Which enzyme does sildenfil citrate (Viagra) inhibit?

A) Adenylcyclase
B) Guanyl cyclase
C) Nitric oxide synthase
D) Phosphodiesterase 5
E) Protein kinase G

Question 49

As regards receptor? mediated hydrolysis of phosphatidylinositol, which of the following statements, if any, is/are true?

A) Activated Protein Kinase C activates the transcription factor NF Kappa B by directly phosphorylating it which allows its release from I Kappa B (the cytosolic inhibitor).
B) Protein Kinase C activity is directly stimulated by calcium and IP3.
C) In receptors coupled to the PI cycle but not containing an intrinsic tyrosine kinase activity, the two second messengers of the PI cycle are released by the enzyme phospholipase C Gamma?l
D) All of the above.
E) None of the above.

Question 50

Which is a protein that can be translocated from cytosol to nucleus during cytokine-initiated signaling?

A) Interferon
B) JAK
C) NFkB
D) SMAD
E) Src

Question 51

Using the figure above, where does phospholipase C cleave?

A) A
B) B
C) C
D) D
E) E

Question 52

Inositol 1,4,5-trisphosphate

A) binds to a specific site on protein kinase A.
B) binds to a specific site on phosphoprotein phosphatase.
C) is formed by three phosphorylations of inositol in the presence of ATP.
D) regulates a Ca²⁺ channel in the endoplasmic reticulum.

Question 53

An intracellular signal transducing ion for many hormones is

A) bicarbonate.
B) calcium.
C) chloride.
D) magnesium.
E) phosphate.

Question 54

Which of the following neurotransmitters would promote chloride entry into the post-synaptic terminal?

A) Acetylcholine
B) ATP
C) GABA
D) Glutamate
E) Serotonin

Question 55

What is an example of a lipid second messenger?

A) Calcium
B) cAMP
C) cGMP
D) Diacylglycerol
E) Inositol phosphate

Question 56

A gain of function mutation to a gene encoding a protein in a signal transduction pathway

A) cannot involve the genes encoding heterotrimeric guanine nucleotide-binding proteins.
B) causes constitutive activation of signal transduction.
C) is characterized by a measurable increase in the circulating concentration of the specific hormone agonist.
D) is invariably germ?line in origin.

Question 57

5Inositol 1,4,5-trisphosphate (IP3)

A) is a long-lived messenger of hormone action.
B) causes the rapid release of calcium from intracellular stores.
C) is a product of a protein kinase C reaction.
D) cannot undergo further phosphorylation.
E) is essential for the action of calmodulin.

Question 58

Initial communication of environmental stimuli to the intracellular milieu via receptor-ligand binding is called

A) extracellular signaling.
B) cellular response.
C) intracellular transmission.
D) contact inhibition.
E) exocytosis.

Question 59

During signal transduction, fluctuations in the concentration of cytosolic calcium are controlled by

A) calmodulin and phospholipase C.
B) gated Ca²⁺ channels and Ca²⁺-ATPase.
C) parathyroid hormone and calcitonin.
D) protein kinase and phosphoprotein phosphatase.

Question 60

What happens when SMADs dimerize?

A) A protein kinase activity is revealed and SMAD autophosphorylates
B) Nuclear location sequences are exposed
C) SH3 domains bind
D) The βγ subunits dissociate from the α subunit
E) The folding of SMAD becomes more compact

Question 61

Which neurotransmitter is inactivated by an ectoenzyme?

A) Acetylcholine
B) GABA
C) Glutamate
D) Glycine
E) Serotonin

Question 62

The amount of phospahtidylinositol-4,5-bisphosphate in the membrane is too small to fill the need for prolonged signaling. What is an alternative source of diacylglycerol?

A) Acetyl CoA
B) Cardiolipin
C) Intracellular IP2
D) Phosphatidyl choline and ethanolamine
E) Triacylglycerols

Question 63

Formation of a GDP-gamma alpha subunit complex (gamma alpha GDP)

A) follows phosphorylation of the gamma subunit.
B) increases association with target proteins.
C) is stimulated by hydrolysis-resistant analogs of GTP.
D) precedes assembly of the gamma heterotrimer.
E) requires hydrolysis of ATP.

Question 64

How many kinase steps are there from activation of the Ras protein to, and including, phosphorylation of the final target protein?

A) 1
B) 2
C) 3
D) 4
E) 5

Question 65

In the figure above which letter represents K_D?

A) A
B) B
C) C
D) D

Question 66

Certain bacterial exotoxins, such as cholera and pertussis, are useful in defining the steps and proteins in signal transduction pathways. Which of the following reactions best accounts for this toxin property?

A) activation of specific lipid kinases
B) covalent modification of heterotrimeric G proteins
C) high?affinity binding to nuclear receptors
D) inhibition of cyclic nucleotide hydrolysis
E) rapid release of Ca²⁺ into cytosol

Question 67

What is the major signaling molecule that binds to soluble guanylate cyclase?

A) cAMP
B) Epinephrine
C) Glucagon
D) Insulin
E) NO

Question 68

Why does the rapid reduction in ligand concentration play a role in terminating cell response in synaptic signaling, and not in endocrine signaling?

A) Antagonists are also present in the synapse
B) Hormones do not have degradative pathways
C) The receptors can be up-regulated in the synapse
D) The volume of the ligand environment is lower in the synapse
E) There is no regulation of hormone synthesis

Question 69

Why is the hydrolysis of GTP by a G-protein essentially irreversible?

A) GDP immediately hydrolyzes to GMP and Pi
B) GDP is metabolized to cGMP
C) GDP remains bound after Pi is liberated
D) GTP cannot be synthesized from GDP
E) The Km for Pi is too low

Question 70

How does protein kinase A effect responses at the level of transcription?

A) It binds a cAMP-sensitive regulatory element (CRE)
B) It phosphorylates CREBs (cAMP-regulated gene regulatory proteins)
C) PKA phosphorylates a small molecule that enters the nucleus and binds CRE
D) The regulatory subunits deactivate repressors
E) The regulatory subunits of the enzyme enter the nucleus and bind DNA

Question 71

Which form of phosphatidylinositol phosphate is the precursor of IP3?

A) Monophospho
B) Bisphospho
C) Trisphospho
D) Tetrakisphospho
E) Pentaphospho

Question 72

What is the function of rapsyn?

A) Antagonist for glutamate
B) Concentrate acetylcholine receptors in membrane
C) Degrade GABA
D) Inactivator of voltage-gated channels
E) Reuptake of serotonin

Question 73

What class of compounds inhibit phosphodiesterases, thereby raising cAMP levels?

A) Guanidinium
B) Indoles
C) Pyrimidines
D) Pyrroles
E) Xanthines

Question 74

What is a function of the G-protein βγ dimer?

A) As an anchor protein in the membrane
B) Exchange of GTP for GDP
C) Hydrolysis of GTP
D) Regulation of ion channel opening
E) Regulation of phosphodiesterase activity

Question 75

What type of signaling do prostaglandins use?

A) Autocrine
B) Endocrine
C) Juxtacrine
D) Pilus
E) Synaptic

Question 76

What is the most common mechanism for deactivation of the hormone receptor in G-protein-associated signaling?

A) Degradation of hormone
B) Degradation of receptor
C) GTP hydrolysis
D) Phosphorylation of receptor
E) Receptor internalization

Question 77

GTP is essential in the hormone mediated production of cAMP. Its role is to

A) stimulate the activity of aspartate transcarbamoylase.
B) increase the cellular level of ATP by serving as a substrate in the synthesis of ATP.
C) bind to the G-protein forming a complex which is necessary for the activation of adenylate cyclase.
D) bind to EF-tu forming a complex necessary for the insertion of ATP into the A-site.

Question 78

What is the term used to indicate the mechanism of protein kinase cascades?

A) Addition
B) Amplification
C) Increase
D) Logarithmic
E) Multiplication