Chapter 8: Cell Signaling Systems

A ligand binds to a transmembrane protein. This causes a conformational change in the

protein that is detected by an intracellular protein. The intracellular protein is an enzyme that

adds phosphate groups to target proteins. The phosphorylated proteins cause a physiological

change within the cell. This is an example of

a signal transduction pathway

Which of the following does NOT participate in a signal transduction pathway?

a. second messenger

b. first messenger

c. receptor protein

d. lipid transporter

lipid transporter

Construct a functional signal transduction pathway by placing the following actors in the

correct order:

A. upstream signaling protein

B. second messenger

C. receptor protein

D. first messenger

E. target proteins

F. downstream signaling protein

D, C, A, B, F, E

First messengers, but NOT second messengers

are located extracellularly

Which of the following is an example of a first or second messenger?

a. peptide hormone

b. G protein-coupled receptor

c. protein kinase

d. cyclic nucleotide phosphodiesterase

peptide hormone

Which of the following list includes ONLY first messengers?

a. cortisol, insulin, prostaglandins

b. nitric oxide, estradiol, heme

c. insulin, glucagon, glucose

d. Ca2+, testosterone, protein kinase A

cortisol, insulin, prostaglandins

Estradiol is secreted by the ovaries, travels through the bloodstream, and interacts with

estrogen receptors on breast epithelial cells. In this scenario estradiol is acting through which

type of mechanism?

endocrine

A Western blot analysis of the expression of estrogen receptors in ovarian tissues at different

times of the estrous cycle showed approximately four times greater protein levels at day 2

compared with day 10 of the cycle. Which of the following may be true given these data?

a. Estrogen is acting as an endocrine signal in the ovaries.

b. Estrogen is acting as an autocrine signal in the ovaries.

c. Ovaries only secrete estrogen early in the estrous cycle.

d. Ovarian tissue is responsive to estrogen only early in the estrous cycle.

Estrogen is acting as an autocrine signal in the ovaries

Acetylcholine is a neurotransmitter that stimulates muscle contraction. Acetylcholine is

acting as a(n)

paracrine signal

Cyclic GMP is the __________ during vasodilation

second messenger

Muscle relaxation in response to nitric oxide would be reduced if a(n) __________ was

present.

stimulator of cGMP phosphodiesterase

The levels of the second messenger involved in vasodilation are increased by __________ and

decreased by __________.

guanylate cyclase; cGMP phosphodiesterase

Which class of proteins interacts with a heterotrimeric intracellular protein?

G protein-coupled receptors

Ligand binding causes which of the following to form trimers?

a. tumor necrosis factor receptors

b. receptor tyrosine kinases

c. G protein-couplesd receptors

d. nicotinic acetylcholine receptors

tumor necrosis factor receptors

What characteristic is true for both RTKs and GPCRs?

The receptor undergoes a conformational change on activation.

Which of the following is a GTPase?

a. Gβ

b. Gγ

c. Gsα

d. Gβγ

Gsα

The α subunit of trimeric G proteins can function to

activate adenylate cyclase.

Levels of diacylglycerol increase in a cell on binding of a ligand to a taste receptor. Which

trimeric G protein subunit is most likely to be bound to GTP?

Gqα

Which of the following is activated or increased in a liver cell on exposure to either glucagon

or epinephrine?

cAMP

An estrogen-dependent breast cancer cell line is grown in a medium that contains estrogen.

Cell proliferation is monitored over time. In a separate experiment, the cell line is grown in a

medium that lacks estrogen but includes bisphenol A, a compound found in polycarbonate

plastics. When monitored, cell proliferation is higher than in the presence of estrogen. A

possible explanation of these results is that bisphenol A

is an antagonist of the estrogen receptor

Which of the following compounds is a pharmaceutical adrenergic receptor agonist?

a. dopamine

b. metoprolol

c. norepinephrine

d. clonidine

clonidine

When bound to GTP, GSα obtains a conformation that promotes interaction with

adenylate cyclase.

When the regulatory subunit of PKA is bound to cAMP,

it cannot bind to catalytic subunit of PKA.

When PKA is inactive, which of the following is true?

a. The pseudosubstrate of the PKA regulatory subunits is bound in the active site of the

catalytic subunits.

b. The regulatory subunits are bound by cAMP.

c. The regulatory subunits are bound by GTP.

d. ATP is unable to bind the catalytic subunits.

The pseudosubstrate of the PKA regulatory subunits is bound in the active site of the

catalytic subunits

Liver cells were monitored for changes in metabolic enzymatic activity after exposure to

glucagon. The enzymes that showed changes in activity were then analyzed to assess if they

had been covalently modified. Which of the following results were likely observed?

a. Enzymes that showed lower activity were not phosphorylated.

b. Enzymes that showed higher activity were methylated.

c. Enzymes that showed altered activity (higher or lower) were phosphorylated.

d. Enzymes that showed altered activity (higher or lower) were methylated.

Enzymes that showed altered activity (higher or lower) were phosphorylated

If protein kinase A is activated in a liver cell in response to glucagon binding to the

β2-adrenergic receptor, which of the following will result?

a. Glycogen synthesis will be turned on.

b. Glycogen degradation will be turned on.

c. Glucose synthesis will be turned off.

d. GLUT1 expression will be upregulated.

Glycogen degradation will be turned on.

Which of the following prevents GPCR from reassociating with the Gαβγ complex?

a. β-arrestin

b. GTPase activating protein

c. cAMP phosphodiesterase

d. RGS

β-arrestin

The __________ is a specific type of __________.

a. GRK; βARK

b. β-adrenergic receptor kinase; β-arrestin

c. regulator of G protein signaling; GTPase activating protein

d. GTPase activating protein; guanine nucleotide exchange factor

regulator of G protein signaling; GTPase activating protein

Which scenario would allow β-arrestin to bind to the GPCR?

a. βARK is internalized into the endosome.

b. The receptor is phosphorylated.

c. Gα is bound to GDP.

d. The regulatory subunit of β-arrestin is removed.

The receptor is phosphorylated.

Place the following steps in proper order:

A. phosphorylation of RTK cytoplasmic tails

B. activation of downstream signaling pathways

C. ligand binding, receptor dimerization, and kinase activation

D. protein binding to RTK phosphotyrosines and phosphorylation of target proteins

C, A, D, B

If there were a technique that allowed one to isolate EGFR1 and EGFR2 at discrete steps along

their activation pathway, which of the following would be isolated?

a. A dimer in which EGFR2 contains phosphotyrosines but EGFR1 does not.

b. A dimer in which EGFR1 contains phosphotyrosines but EGFR2 does not.

c. A monomer of EGFR1 that contains phosphotyrosines.

d. A monomer of EGFR2 that contains phosphotyrosines.

A dimer in which EGFR2 contains phosphotyrosines but EGFR1 does not.

Which of the following proteins contains an SH3 domain?

a. growth factor receptor-bound 2 (GRB2)

b. phosphoinositide-3 kinase (PI-3K)

c. SOS protein

d. RasGAP

growth factor receptor-bound 2 (GRB2)

If GRB2 were truncated so that the N-terminal domain was missing, the truncated protein

would be unable to bind the

proline-rich sequence of the SOS protein.

Which of the following is true of a recessive oncogene mutation but NOT a dominant

oncogene mutation?

a. It results in a disease phenotype any time the mutation is present in a cell.

b. It results in a disease phenotype only when both copies of the mutated oncogene are

present in the same cell.

c. It is a gain-of-function mutation.

d. It is a mutation in a tumor suppressor gene.

It results in a disease phenotype only when both copies of the mutated oncogene are

present in the same cell

A mutation causes a cell to divide uncontrollably. Analysis of the cell shows that both copies

of the gene must have the mutation. From this information, it can be determined that the

mutation is

recessive

The insulin receptor is a type of

receptor tyrosine kinase

On binding of an insulin molecule to the insulin receptor, a conformational change occurs that

stimulates tyrosine autophosphorylation in the β subunits.

Construct a functional pathway out of the following steps.

A: Phosphorylation of β subunits of the insulin receptor occurs.

B: Insulin binds to α subunits of the insulin receptor.

C: PI-3K is activated.

D: IRS is phosphorylated.

B, A, D, C

On insulin binding to the insulin receptor, MAP kinase signaling proteins are activated. Which

of the following proteins are part of this signaling pathway?

a. Shc

b. IRS

c. PI-3K

d. GLUT-1

Shc

Which of the following occurs after activation of the PI-3K signaling pathway?

a. Glycogen synthesis rates decrease.

b. GRB2 is activated.

c. GLUT-1 levels decrease.

d. Glucose uptake increases

Glucose uptake increases

A new protein is discovered that contains a pleckstrin homology domain. Which of the

following is likely to bind to the protein?

a. PIP3

b. PI-3K

c. phosphorylated tyrosines

d. Ca2+

PIP3

Caspases contain

an active site cysteine residue.

A caspase is a

protease

Caspase 3 is responsible for

degrading key regulatory molecules.

If a mutation occurred in SODD that prohibited its interaction with the DD of TNF receptor,

the TNF receptor would

bind TRADD, even in the absence of TNF-α.

Both the silence of death domain and TNF receptor-associated death domain proteins

bind TNF receptor death domains

Which protein is part of the TNF receptor-activated programmed cell death signaling

pathway?

FADD

Place the following steps of the apoptotic pathway in their proper order.

A. CASP3 cleavage of cellular proteins

B. Cleavage of procaspase 8

C. Cleavage of procaspase 3

D. Assembly of DD and DED protein complexes

D, B, C, A

Which of the following acts as a transcription factor in the cell survival pathway activated by

TNF-α?

a. p50:p65 complex

b. NIK:RIP complex

c. IκBα

d. IKK

p50:p65 complex

Phosphorylation of which of the following is necessary for the increased expression of

antiapoptotic genes?

a. RIP

b. TNF receptor

c. FADD

d. IKK

IKK

Which of the following is true of active NFκB?

a. It is a dimer.

b. It is phosphorylated.

c. It is in a complex with a DD.

d. It has been proteolytically activated.

It is a dimer.

Consider a mutant cell that does not form DISC on TNF signaling. Which of the following

would occur in this mutant cell if exposed to TNF-α?

a. Caspase 3 would be activated.

b. TNF-α would bind to the TNF receptor.

c. Caspase 8 would be activated.

d. The cell would undergo apoptosis.

TNF-α would bind to the TNF receptor.

Which of the following is true of procaspase 8?

a. It is proteolytically active.

b. It can cleave caspase 3.

c. It can be activated by proteolysis.

d. It is a kinase.

It can be activated by proteolysis.

Consider a mutation in procaspase 3 that changes Asp28 to an amino acid that is no longer a

substrate for autocleavage. This mutant would

be partially activated.

Cell-specific responses to signaling molecules are possible because

nuclear receptor expression is cell specific.

Cultures of two different cell types are exposed to the same signaling ligand. Analysis of gene

expression shows that only one of the cell types responded to the ligand. Which of the

following may account for this difference?

a. The ligand was only bioavailable to one of the cell types.

b. Only one of the cell types contained accessible target gene DNA sequences.

c. Only one cell type contained DNA.

d. The ligand could only pass through the membrane of one of the cell types.

Only one of the cell types contained accessible target gene DNA sequences.

Which of the following DNA sequences is MOST likely to be bound by a steroid receptor?

a. AGGAGAACATCATGTTCT

b. AGGAGATAGGAGAACT

c. TTTGATCCAGTTTCCAGT

d. CCCAAGTTCCCAAG

AGGAGAACATCATGTTCT

Which of the following is a metabolite receptor?

a. aldosterone receptor

b. glucocorticoid receptor

c. progesterone receptor

d. thyroid hormone receptor

thyroid hormone receptor

The ligands for metabolite receptors are often derived from dietary nutrients, including all

EXCEPT which of the following?

a. essential amino acids

b. vitamins

c. unsaturated fatty acids

d. saturated fatty acids

saturated fatty acids

The PPARγ-RXRα heterodimer interacts with DNA via

zinc finger motifs

Removal of which metal ion would likely alter the structure of the GR DNA-binding domain

and preclude it from binding to DNA?

Zn2+

A class of proteins that assist other proteins to fold are known as __________ proteins.

chaperonin

Hsp90 is a type of

chaperonin

A response element is

a sequence of regulatory DNA

Which of the following is NOT an expected effect of the binding of the glucocorticoid

response element by GR?

a. upregulation of annexin I

b. inhibition of the inflammatory response

c. upregulation of cyclooxygenase-2

d. decreased interaction of p65 and p50 of NFκB

upregulation of cyclooxygenase-2

The __________ domain functions as a protein-protein interaction module and is located in

the cytoplasmic tail of TNF receptors

death

The result of TRADD proteins binding to TNF receptors is that

an activated adaptor complex is formed.