CHAPTER 16
CELL COMMUNICATION
 2009 Garland Science Publishing
General Principles of Cell Signaling
16-1
Cell lines A and B both survive in tissue culture containing serum but do not
proliferate. Factor F is known to stimulate proliferation in cell line A. Cell line A
produces a receptor protein (R) that cell line B does not produce. To test the role
of receptor R, you introduce this receptor protein into cell line B, using
recombinant DNA techniques. You then test all of your various cell lines in the
presence of serum for their response to factor F, with the results summarized in
Table Q16–1.
Table Q16-1
Which of the following cannot be concluded from your results above?
(a)
Binding of Factor F to its receptor is required for proliferation of cell line
A.
(b)
Receptor R binds to Factor F to induce cell proliferation in cell line A.
(c)
Cell line A expresses a receptor for Factor F.
(d)
Factor F is not required for proliferation in cell line B.
16-2
For each of the following sentences, fill in the blanks with the best word or phrase
selected from the list below. Not all words or phrases will be used; each word or
phrase should be used only once.
Cells can signal to each other in various ways. A signal that must
be relayed to the entire body is most efficiently sent by
__________________ cells, which produce hormones that are
carried throughout the body through the bloodstream. On the other
hand, __________________ methods of cell signaling do not
require the release of a secreted molecule and are used for very
localized signaling events. During __________________
signaling, the signal remains in the neighborhood of the secreting
cell and thus acts as a local mediator on nearby cells. Finally,
__________________ signaling converts electrical impulses into a
chemical signal. Cells receive signals through a
__________________, which can be an integral membrane protein
or can reside inside the cell.
amplification
contact-dependent
endocrine
epithelial
G-protein
K+ channel
neuronal
paracrine
phosphorylation
receptor
target
16-3
Rank the following types of cell signaling from 1 to 4, with 1 representing the
type of signaling in which the signal molecule travels the least distance and 4 the
type of signaling in which the signal molecule travels the largest distance.
______ paracrine signaling
______ contact-dependent signaling
______ neuronal signaling
______ endocrine signaling
16-4
Explain why the signal molecules used in neuronal signaling work at a longer
range than those used in contact-dependent signaling.
16-5
Circle the phrase in each pair that is likely to occur more rapidly in response to an
extracellular signal.
A.
changes in cell secretion / increased cell division
B.
changes in protein phosphorylation / changes in proteins being synthesized
C.
changes in mRNA levels / changes in membrane potential
16-6
Receipt of extracellular signals can change cell behavior quickly (e.g., in seconds
or less) or much more slowly (e.g., in hours).
A.
What kind of molecular changes could cause quick changes in cell
behaviour?
B.
What kind of molecular changes could cause slow changes in cell
behaviour?
C.
Explain why the response you named in A results in a quick change,
whereas the response you named in B results in a slow change.
16-7
Which of the following statements is false?
(a)
Nucleotides and amino acids can act as extracellular signal molecules.
(b)
Some signal molecules can bind directly to intracellular proteins that bind
DNA and regulate gene transcription.
(c)
Some signal molecules are transmembrane proteins.
(d)
Dissolved gases such as nitric oxide (NO) can act as signal molecules, but
because they cannot interact with proteins they must act by affecting
membrane lipids.
16-8
All members of the steroid hormone receptor family __________________.
(a)
are cell-surface receptors
(b)
(c)
(d)
do not undergo conformational changes
are found only in the cytoplasm
interact with signal molecules that diffuse through the plasma membrane
16-9
Figure Q16-9
Given the generic signaling pathway in Figure Q16-9, write the number
corresponding to the item on the line next to the descriptor below.
_________
_________
_________
_________
receptor protein
effector proteins
intracellular signaling proteins
ligand
16-10 The lab you work in has discovered a previously unidentified extracellular signal
molecule called QGF, a 75,000-dalton protein. You add purified QGF to different
types of cells to determine its effect on these cells. When you add QGF to heart
muscle cells, you observe an increase in cell contraction. When you add it to
fibroblasts, they undergo cell division. When you add it to nerve cells, they die.
When you add it to glial cells, you do not see any effect on cell division or
survival. Given these observations, which of the following statements is most
likely to be true?
(a)
Because it acts on so many diverse cell types, QGF probably diffuses
across the plasma membrane into the cytoplasm of these cells.
(b)
Glial cells do not have a receptor for QGF.
(c)
(d)
QGF activates different intracellular signaling pathways in heart muscles,
fibroblasts, and nerve cells to produce the different responses observed.
Heart muscle cells, fibroblasts, and nerve cells must all have the same
receptor for GQF.
16-11 Can signaling via a steroid hormone receptor lead to amplification of the original
signal? If so, how?
16-12 Acetylcholine is a signaling molecule that elicits responses from heart muscle
cells, salivary gland cells, and skeletal muscle cells. Which of the following
statements is false?
(a)
Heart muscle cells decrease their rate and force of contraction when they
receive acetylcholine, whereas skeletal muscle cells contract.
(b)
Heart muscle cells, salivary gland cells, and skeletal muscle cells all
express an acetylcholine receptor that belongs to the transmitter-gated ion
channel family.
(c)
Active acetylcholine receptors on salivary gland cells and heart muscle
cells activate different intracellular signaling pathways.
(d)
Heart muscle cells, salivary gland cells, and skeletal muscle cells all
respond to acetylcholine within minutes of receiving the signal.
16-13 When the neurotransmitter acetylcholine is applied to skeletal muscle cells, it
binds the acetylcholine receptor and causes the muscle cells to contract.
Succinylcholine, which is a chemical analog of acetylcholine, binds to the
acetylcholine receptor on skeletal muscle cells but causes the muscle to relax; it is
therefore often used by surgeons as a muscle relaxant. Propose a model for why
succinylcholine causes muscle relaxation. What might be the mechanism to
explain the different activities of acetylcholine and succinylcholine on the
acetylcholine receptor?
16-14 The local mediator nitric oxide stimulates the intracellular enzyme guanylyl
cyclase by ________________.
(a)
activating a G-protein
(b)
activating a receptor tyrosine kinase
(c)
diffusing into cells and stimulating the cyclase directly
(d)
activating an intracellular protein kinase
16-15 Figure Q16-15 shows the pathway through which nitric oxide (NO) triggers
smooth muscle relaxation in a blood-vessel wall. Which of the following
situations would lead to relaxation of the smooth muscle cells in the absence of
acetylcholine?
Figure Q16-15
(a)
(b)
(c)
(d)
a smooth muscle cell that has a defect in guanylyl cyclase such that it
cannot bind NO
a muscle cell that has a defect in guanylyl cyclase such that it
constitutively converts GTP to cyclic GMP
a muscle cell that has cyclic GMP phosphodiesterase constitutively active
a drug that blocks an enzyme involved in the metabolic pathway from
arginine to NO
16-16 For each of the following sentences, select the best word or phrase from the list
below to fill in the blanks. Not all words or phrases will be used; each word or
phrase should be used only once.
An extracellular signal molecule can act to change a cell’s
behavior by acting through cell-surface __________________ that
control intracellular signaling proteins. These intracellular
signaling proteins ultimately change the activity of
__________________ proteins that bring about cell responses.
Intracellular signaling proteins can __________________ the
signal received to evoke a strong response from just a few
extracellular signal molecules. A cell that receives more than one
extracellular signal at the same time can __________________ this
information using intracellular signaling proteins.
__________________ proteins can act as molecular switches,
letting a cell know that a signal has been received. Enzymes that
phosphorylate proteins, termed ___________, can also serve as
molecular switches; the actions of these enzymes are countered by
the activity of __________________.
GMP-binding
GTP-binding
protein phosphatases
neurotransmitter
amplify
effector
decrease
esterases
integrate
AMP-binding
cleavage
decouple
sterols
convolute
protein kinases
acetylase
receptors
autocrine
16-17 Name the three main classes of cell-surface receptor.
16-18 Which of the following statements is true?
(a)
Extracellular signal molecules that are hydrophilic must bind to a cellsurface receptor so as to signal a target cell to change its behavior.
(b)
To function, all extracellular signal molecules must be transported by their
receptor across the plasma membrane into the cytosol.
(c)
A cell-surface receptor capable of binding only one type of signal
molecule can mediate only one kind of cell response.
(d)
Any foreign substance that binds to a receptor for a normal signal
molecule will always induce the same response that is produced by that
signal molecule on the same cell type.
16-19 Which of the following statements about molecular switches is false?
(a)
Phosphatases remove the phosphate from GTP on GTP-binding proteins,
turning them off.
(b)
Protein kinases transfer the terminal phosphate from ATP onto a protein.
(c)
Serine/threonine kinases are the most common types of protein kinase.
(d)
A GTP-binding protein exchanges its bound GDP for GTP to become
activated.
16-20 Intracellular steroid hormone receptors have binding sites for a signaling molecule
and a DNA sequence. How is it that the same steroid hormone receptor, which
binds to a specific DNA sequence, can regulate different genes in different cell
types?
16-21 Your friend is studying a segment of a newly discovered virus that carries an
enhancer of gene expression that confers responsiveness to glucocorticoid (a
hormone) on genes that are linked to it. He constructs two versions of a reporter
gene: one has only a minimal promoter linked to it (which contains sites for RNA
polymerase binding); the other reporter gene has both this minimal promoter plus
the viral enhancer attached to it. The reporter gene allows him to measure the
amount of transcription that occurs from each construct. Your friend puts each of
these constructs into two different cell lines and examines the expression of the
reporter gene in each cell line, as shown in Figure Q16-21. He is puzzled by these
findings and asks for your help in interpreting them.
Figure Q16-21
A.
B.
From these data, can you tell whether both cell lines contain
glucocorticoid receptors? Why?
What might account for the difference in the transcription of the reporter
gene in cell lines 1 and 2 after introduction of the construct containing the
viral enhancer in the presence of glucocorticoid?
G-Protein-Coupled Receptors
16-22 For each of the following sentences, select the best word or phrase from the list
below to fill in the blanks. Not all words or phrases will be used; each word or
phrase should be used only once.
G-protein-coupled receptors (GPCRs) all have a similar structure
with __________________ transmembrane domains. When a
GPCR binds an extracellular signal, an intracellular G protein,
composed of __________________ subunits, becomes activated.
__________________ of the G-protein subunits are tethered to the
plasma membrane by short lipid tails. When unstimulated, the α
subunit is bound to __________________, which is exchanged for
__________________ on stimulation. The intrinsic
__________________ activity of the α subunit is important for
inactivating the G protein. __________________ inhibits this
activity of the α subunit, thereby keeping the subunit in an active
state.
phosphodiesterase
GTP
seven
four
GDP
diacylglycerol
five
adenylyl cyclase
cholera toxin
AMP
three
ATPase
ATP
GTPase
Ca2+
twelve
cAMP
two
16-23 Indicate by writing “yes” or “no” whether amplification of a signal could occur at
the particular steps described below. Explain your answers.
A.
An extracellular signaling molecule binds and activates a GPCR.
B.
The activated GPCRs cause Gα to separate from Gβ and Gγ.
C.
Adenylyl cyclase produces cyclic AMP.
D.
cAMP activates protein kinase A.
E.
Protein kinase A phosphorylates target proteins.
16-24 The following happens when a cell-surface receptor activates a G protein.
(a)
The β subunit exchanges its bound GDP for GTP.
(b)
The GDP bound to the α subunit is phosphorylated to form bound GTP.
(c)
The α subunit exchanges its bound GDP for GTP.
(d)
It activates the α subunit and inactivates the βγ complex.
16-25 Acetylcholine binds to a GPCR on heart muscle, making the heart beat more
slowly. The activated receptor stimulates a G protein, which opens a K+ channel
in the plasma membrane, as shown in Figure Q16-25. Which of the following
would enhance this effect of the acetylcholine?
Figure Q16-25
(a)
(b)
(c)
(d)
addition of a high concentration of a non-hydrolyzable analog of GTP
addition of a drug that prevents the α subunit from exchanging GDP for
GTP
mutations in the acetylcholine receptor that weaken the interaction
between the receptor and acetylcholine
mutations in the acetylcholine receptor that weaken the interaction
between the receptor and the G protein
16-26 Acetylcholine acts at a GPCR on heart muscle to make the heart beat more
slowly. It does so by ultimately opening K+ channels in the plasma membrane (as
diagrammed in Figure Q16-25), which decreases the cell’s excitability by making
it harder to depolarize the plasma membrane.
Indicate whether each of the following conditions would increase or decrease the
effect of acetylcholine.
A.
addition of a drug that stimulates the GTPase activity of the Gα subunit
B.
mutations in the K+ channel that keep it closed all the time
C.
D.
E.
F.
modification of the Gα subunit by cholera toxin
a mutation that decreases the affinity of the βγ complex of the G protein
for the K+ channel
a mutation in the acetylcholine receptor that prevents its localization on
the cell surface
adding acetylcholinesterase to the external environment of the cell
16-27 During the mating process, yeast cells respond to pheromones secreted by other
yeast cells. These pheromones bind GPCRs on the surface of the responding cell
and lead to the activation of G proteins inside the cell. When a wild-type yeast
cell senses the pheromone, its physiology changes in preparation for mating: the
cell stops growing until it finds a mating partner. If yeast cells do not undergo the
appropriate response after sensing a pheromone, they are considered sterile. Yeast
cells that are defective in one or more components of the G protein have
characteristic phenotypes in the absence and presence of the pheromone, which
are listed in Table 16-27.
Table Q16-27 Mating phenotypes of various strains of yeast
Which of the following models is consistent with the data from the analysis of
these mutants? Explain your answer.
(a)
α activates the mating response but is inhibited when bound to βγ.
(b)
βγ activates the mating response but is inhibited when bound to α.
(c)
The G protein is inactive; either free α or free βγ complex is capable of
activating the mating response.
(d)
The G protein is active; both free α and free βγ complex are required to
inhibit the mating response
16-28 You are interested in how cyclic-AMP-dependent protein kinase A (PKA)
functions to affect learning and memory, and you decide to study its function in
the brain. It is known that, in the cells you are studying, PKA works via a signal
transduction pathway like the one depicted in Figure Q16-28. Furthermore, it is
also known that activated PKA phosphorylates the transcriptional regulator called
Nerd that then activates transcription of the gene Brainy. Which situation
described below will lead to an increase in Brainy transcription?
Figure Q16-28
(a)
(b)
(c)
(d)
a mutation in the Nerd gene that produces a protein that cannot be
phosphorylated by PKA
a mutation in the nuclear import sequence of PKA from PPKKKRKV to
PPAAAAAV
a mutation in the gene that encodes cAMP phosphodiesterase that makes
the enzyme inactive
a mutation in the gene that encodes adenylyl cyclase that renders the
enzyme unable to interact with the α subunit of the G protein
16-29 Adrenaline stimulates glycogen breakdown in skeletal muscle cells by ultimately
activating glycogen phosphorylase, the enzyme that breaks down glycogen, as
depicted in Figure Q16-29.
Figure Q16-29
Which of the following statements below is false?
(a)
A constitutively active mutant form of PKA in skeletal muscle cells would
lead to a decrease in the amount of unphosphorylated phosphorylase
kinase.
(b)
A constitutively active mutant form of PKA in skeletal muscle cells would
not increase the affinity of adrenaline for the adrenergic receptor.
(c)
A constitutively active mutant form of PKA in skeletal muscle cells would
lead to an excess in the amount of glucose available.
(d)
A constitutively active mutant form of PKA in skeletal muscle cells would
lead to an excess in the amount of glycogen available.
16-30 Activated protein kinase C (PKC) can lead to the modification of the membrane
lipids in the vicinity of the active PKC. Figure Q16-30 shows how G proteins can
indirectly activate PKC. You have discovered the enzyme activated by PKC that
mediates the lipid modification. You call the enzyme Rafty and demonstrate that
activated PKC directly phosphorylates Rafty, activating it to modify the plasma
membrane lipids in the vicinity of the cell where PKC is active; these lipid
modifications can be detected by dyes that bind to the modified lipids. Cells
lacking Rafty do not have these modifications, even when PKC is active. Which
of the following conditions would lead to signal-independent modification of the
membrane lipids by Rafty?
Figure Q16-30
(a)
(b)
(c)
(d)
the expression of a constitutively active phospholipase C
a mutation in the GPCR that binds the signal more tightly
a Ca2+ channel in the endoplasmic reticulum with an increased affinity for
IP3
a mutation in the gene that encodes Rafty such that the enzyme can no
longer be phosphorylated by PKC
16-31 A calmodulin-regulated kinase (CaM-kinase) is involved in spatial learning and
memory. This kinase is able to phosphorylate itself such that its kinase activity is
now independent of the intracellular concentration of Ca2+. Thus the kinase stays
active after Ca2+ levels have dropped. Mice completely lacking this CaM-kinase
have severe spatial learning defects but are otherwise normal.
A.
Each of the following mutations also leads to similar learning defects. For
each case explain why.
(1)
a mutation that prevents the kinase from binding ATP
(2)
a mutation that deletes the calmodulin-binding part of the kinase
(3)
a mutation that destroys the site of autophosphorylation
B.
What would be the effect on the activity of CaM-kinase if there were a
mutation that reduced its interaction with the protein phosphatase
responsible for inactivating the kinase?
16-32 Activated GPCRs activate G proteins by reducing the strength of binding of GDP
to the α subunit of the G protein, allowing GDP to dissociate and GTP (which is
present at much higher concentrations in the cell than GDP) to bind in its place.
How would the activity of a G protein be affected by a mutation that reduces the
affinity of the α subunit for GDP without significantly changing its affinity for
GTP?
16-33 When adrenaline binds to adrenergic receptors on the surface of a muscle cell, it
activates a G protein, initiating an intracellular signaling pathway in which the
activated α subunit activates adenylyl cyclase, thereby increasing cAMP levels in
the cell. The cAMP molecules then activate a cAMP-dependent kinase (PKA)
that, in turn, activates enzymes that result in the breakdown of muscle glycogen,
thus lowering glycogen levels. You obtain muscle cells that are defective in
various components of the signaling pathway. Referring to Figure Q16-29,
indicate how glycogen levels would be affected in the presence of adrenaline in
the following cells. Would they be higher or lower than in normal cells treated
with adrenaline?
A.
cells that lack adenylyl cyclase
B.
cells that lack the GPCR
C.
cells that lack cAMP phosphodiesterase
D.
cells that have an α subunit that cannot hydrolyze GTP but can interact
properly with the β and γ subunits
16-34 The rod photoreceptors in the eye are extremely sensitive to light. The cells sense
light through a signal transduction cascade involving light activation of a GPCR
that activates a G protein that activates cyclic GMP phosphodiesterase. How
would you expect the addition of the following drugs to affect the light-sensing
ability of the rod cells? Explain your answers.
A.
a drug that inhibits cyclic GMP phosphodiesterase
B.
a drug that is a nonhydrolyzable analog of GTP
16-35 Match the target of the G protein with the appropriate signaling outcome.
adenylyl cyclase ________
ion channels _________
phospholipase C _________
A. cleavage of inositol phospholipids
B. increase in cAMP levels
C. changes in membrane potential
16-36 For each of the following sentences, fill in the blanks with the best word or phrase
selected from the list below. Not all words or phrases will be used; each word or
phrase should be used only once.
Ca2+ can trigger biological effects in cells because an unstimulated
cell has an extremely __________________ concentration of free
Ca2+ in the cytosol, compared with its concentration in the
__________________ space and in the __________________,
creating a steep electrochemical gradient. When Ca2+ enters the
cytosol, it interacts with Ca2+-responsive proteins such as
__________________, which also binds diacylglycerol, and
__________________, which activates CaM-kinases.
average
phosopholipase C
peroxisome
adenylyl cyclase
endoplasmic reticulum
extracellular
protein kinase C
high
protein kinase A
calmodulin
nuclear
low
Ca2+
intracellular
colorful
Enzyme-Coupled Receptors
16-37 The growth factor Superchick stimulates the proliferation of cultured chicken
cells. The receptor that binds Superchick is a receptor tyrosine kinase (RTK), and
many chicken tumor cell lines have mutations in the gene that encodes this
receptor. Which of the following types of mutation would be expected to promote
uncontrolled cell proliferation?
(a)
a mutation that prevents dimerization of the receptor
(b)
a mutation that destroys the kinase activity of the receptor
(c)
a mutation that inactivates the protein tyrosine phosphatase that normally
removes the phosphates from tyrosines on the activated receptor
(d)
a mutation that prevents the binding of the normal extracellular signal to
the receptor
16-38 The growth factor RGF stimulates proliferation of cultured rat cells. The receptor
that binds RGF is a receptor tyrosine kinase called RGFR. Which of the following
types of alteration to RGF would be most likely to prevent receptor dimerization?
(a)
a mutation that increases the affinity of RGFR for RGF
(b)
a mutation that prevents RGFR from binding to RGF
(c)
changing the tyrosines that are normally phosphorylated on RGFR
dimerization to alanines
(d)
changing the tyrosines that are normally phosphorylated on RGFR
dimerization to glutamic acid
16-39 A protein kinase can act as an integrating device in signaling if it
___________________.
(a)
phosphorylates more than one substrate
(b)
catalyzes its own phosphorylation
(c)
is activated by two or more proteins in different signaling pathways
(d)
initiates a phosphorylation cascade involving two or more protein kinases
16-40 Antibodies are Y-shaped molecules that have two identical binding sites. Suppose
that you have obtained an antibody that is specific for the extracellular domain of
an RTK. When the antibody binds to the RTK, it brings together two RTK
molecules. If cells containing the RTK were exposed to the antibody, would you
expect the kinase to be activated, inactivated, or unaffected? Explain your
reasoning.
16-41 Which of the following mechanisms is not directly involved in inactivating an
activated RTK?
(a)
dephosphorylation by serine/threonine phosphatases
(b)
dephosphorylation by protein tyrosine phosphatases
(c)
removal of the RTK from the plasma membrane by endocytosis
(d)
digestion of the RTK in lysosomes
16-42 You are interested in cell size regulation and discover that signaling through an
enzyme-coupled receptor is important for the growth (enlargement) of mouse
liver cells. Activation of the receptor activates adenylyl cyclase, which ultimately
leads to the activation of PKA, which then phosphorylates a transcription factor
called TFS on threonine 42. This phosphorylation is necessary for the binding of
TFS to its specific sites on DNA, where it then activates the transcription of Sze2,
a gene that encodes a protein important for liver cell growth. You find that liver
cells lacking the receptor are 15% smaller than normal cells, whereas cells that
express a constitutively activated version of PKA are 15% larger than normal
liver cells. Given these results, predict whether you would expect the cell’s size to
be bigger or smaller than normal cells if cells were treated in the following
fashion.
A.
You change threonine 42 on TFS to an alanine residue.
B.
You create a version of the receptor that is constitutively active.
C.
You add a drug that inhibits adenylyl cyclase.
D.
You add a drug that increases the activity of cyclic AMP
phosphodiesterase.
E.
You mutate the cAMP-binding sites in the regulatory subunits of PKA, so
that the complex binds cAMP more tightly.
16-43 Male cockroaches with mutations that strongly decrease the function of an RTK
called RTKX are oblivious to the charms of their female comrades. This particular
RTK binds to a small molecule secreted by sexually mature females. Most males
carrying loss-of-function mutations in the gene for Ras protein are also unable to
respond to females. You have just read a paper in which the authors describe how
they have screened cockroaches that are mutant in RTKX for additional mutations
that partly restore the ability of males to respond to females. These mutations
decrease the function of a protein that the authors call Z. Which of the following
types of protein could Z be? Explain your answer.
(a)
a protein that activates the Ras protein by causing Ras to exchange GDP
for GTP
(b)
a protein that stimulates hydrolysis of GTP by the Ras protein
(c)
an adaptor protein that mediates the binding of the RTKX to the Ras
protein
(d)
a transcriptional regulator required for the expression of the Ras gene
16-44 For each of the following sentences, fill in the blanks with the best word or phrase
selected from the list below. Not all words or phrases will be used; each word or
phrase should be used only once.
Cells signal to one another in various ways. Some use extracellular
signal molecules that are dissolved gases, such as
__________________, which can diffuse easily into cells. Others
use cytokines, which bind to cytokine receptors. Cytokine
receptors have no intrinsic enzyme activity but are associated with
cytoplasmic tyrosine kinases called __________________s, which
become activated on the binding of cytokine to its receptor and go
on to phosphorylate and activate cytoplasmic transcriptional
regulators called __________________s. Some intracellular
signaling pathways involve chains of protein kinases that
phosphorylate each other, as seen in the __________________
signaling module. Lipids can also relay signals in the cell, as we
observe when phospholipase C cleaves the sugar-phosphate head
off a lipid molecule to generate the two small messenger molecules
__________________ (which remains embedded in the plasma
membrane) and __________________ (which diffuses into the
cytosol).
cyclic GMP
diacylglycerol
IP3
JAK
MAP kinase
NO
Ras
SMAD
STAT
TGF-β
16-45 Which of the following statements is true?
(a)
MAP kinase is important for phosphorylating MAP kinase kinase.
(b)
PI 3-kinase phosphorylates a lipid in the plasma membrane.
(c)
Ras becomes activated when an RTK phosphorylates its bound GDP to
create GTP.
(d)
STAT proteins phosphorylate JAK proteins, which then enter the nucleus
and activate gene transcription.
16-46 When activated by the extracellular signal protein platelet-derived growth factor
(PDGF), the PDGF receptor phosphorylates itself on multiple tyrosines (as
indicated in Figure 16-46A by the circled Ps; the numbers next to these Ps
indicate the amino acid number of the tyrosine). These phosphorylated tyrosines
serve as docking sites for proteins that interact with the activated PDGF-receptor.
These proteins are indicated in the figure, and include the proteins A, B, C, and D.
One of the cell’s responses to PDGF is an increase in DNA synthesis, which can
be measured by the incorporation of radioactive thymidine into the DNA.
To determine which protein or proteins, A, B, C, or D, are responsible for the
activation of DNA synthesis, you construct mutant versions of the PDGF receptor
that retain one or more tyrosine phosphorylation sites. You express these mutant
versions in cells that do not make their own PDGF receptor. In these cells, the
various mutant versions of the PDGF receptor are expressed normally, and, in
response to PDGF binding, become phosphorylated on whichever tyrosines
remain. You measure the level of DNA synthesis in cells that express the various
mutant receptors and obtain the data shown in Figure 16-46B.
Figure Q16-46
A.
B.
C.
From these data, which, if any, of proteins A, B, C, and D are involved in
the stimulation of DNA synthesis by PDGF? Explain your answer.
Which, if any, of these proteins inhibit DNA synthesis? Explain your
answer.
Which, if any, of these proteins seem to have no detectable role in DNA
synthesis? Explain your answer.
16-47 Two protein kinases, PK1 and PK2, work sequentially in an intracellular signaling
pathway. You create cells that contain inactivating mutations in the genes that
encode either PK1 or PK2 and find that these cells no longer respond to a
particular extracellular signal. You also create cells containing a version of PK1
that is permanently active and find that the cells behave as though they are
receiving the signal even when the signal is not present. When you introduce the
permanently active version of PK1 into cells that have an inactivating mutation in
PK2, you find that these cells also behave as though they are receiving the signal
even when no signal is present.
A.
From these results, does PK1 activate PK2 or does PK2 activate PK1?
Explain your answer.
B.
You now create a permanently active version of PK2 and find that cells
containing this version behave as though they are receiving the signal even
when the signal is not present. What do you predict will happen if you
introduce the permanently active version of PK2 into cells that have an
inactivating mutation in PK1?
16-48 Akt promotes the survival of many cells. It is activated by an intracellular
signaling pathway that is triggered by an RTK that activates PI 3-kinase, as
diagrammed in Figure Q16-48.
Figure Q16-48
Which of the following statements is false?
(a)
In the presence of a survival signal, Akt localizes to the plasma membrane
by binding to PIP3.
(b)
In the absence of survival signal, Bad inhibits the cell death inhibitor
protein Bcl2.
(c)
In the presence of survival signal, the cell death inhibitory protein Bcl2 is
active.
(d)
In the absence of survival signal, Bad is phosphorylated.
16-49 The last common ancestor to plants and animals was a unicellular eucaryote.
Thus, it is thought that multicellularity and the attendant demands for cell
communication arose independently in these two lineages. This evolutionary
viewpoint accounts nicely for the vastly different mechanisms that plants and
animals use for cell communication. Fungi use signaling mechanisms and
components that are very similar to those used in animals. Which of the
phylogenetic trees shown in Figure 16-49 does this observation support?
Figure Q16-49
16-50 The ethylene response in plants involves a dimeric transmembrane receptor.
When the receptor is not bound to ethylene, the receptor binds to and activates a
protein kinase, which activates an intracellular signaling pathway that leads to the
degradation of a transcriptional regulator important for transcribing the ethylene
response genes (see Fig. Q16-50). You discover a phosphatase that is important
for ethylene signaling, and you name it PtpE. Plants lacking PtpE never turn on
ethylene-response genes, even in the presence of ethylene. You find that PtpE
dephosphorylates serine 121 on the transcriptional regulator. Furthermore, plants
lacking PtpE degrade the transcriptional regulator in the presence of ethylene.
Figure Q16-50
Which of the following statements below is inconsistent with your data?
(a)
When the transcriptional regulator is phosphorylated, it activates
transcription of the ethylene-response genes.
(b)
When the transcriptional regulator is not phosphorylated, it binds to DNA.
(c)
Activation of the protein kinase that binds to the ethylene receptor leads to
inactivation of PtpE.
(d)
Binding of ethylene to its receptor leads to the activation of PtpE.
16-51 Figure Q16-51 shows that intracellular signaling pathways can be highly
interconnected.
Figure Q16-51
From the information in Figure Q16-51, which of the following statements is
incorrect?
(a)
The GPCR and the RTK both activate phospholipase C.
(b)
Activation of either the GPCR or the RTK will lead to activation of
transcriptional regulators.
(c)
CaM-kinase is only activated when the GPCR is active and not when the
RTK is active.
(d)
Ras is activated only when the RTK is active and not when the GPCR is
active.
How We Know: Untangling Cell Signaling Pathways
16-52 Figure Q16-52 shows how normal signaling works with a Ras protein acting
downstream of an RTK. You examine a cell line with a constitutively active Ras
protein that is always signaling. Which of the following conditions will turn off
signaling in this cell line?
Figure Q16-52
(a)
(b)
(c)
(d)
addition of a drug that prevents protein X from activating Ras
addition of a drug that increases the affinity of protein Y and Ras
addition of a drug that blocks protein Y from interacting with its target
addition of a drug that increases the activity of protein Y
16-53 Your friend is studying mouse fur color and has isolated the GPCR responsible
for determining its color, as well as the extracellular signal that activates the
receptor. She finds that, on addition of the signal to pigment cells (cells that
produce the pigment determining fur color), cAMP levels rise in the cell. She
starts a biotech company, and the company isolates more components of the
signaling pathway responsible for fur color. Using transgenic mouse technology,
the company genetically engineers mice that are defective in various proteins
involved in determining fur color. The company obtains the following results.
Normal mice have beige (very light brown) fur color.
Mice lacking the extracellular signal have white fur.
Mice lacking the GPCR have white fur.
Mice lacking cAMP phosphodiesterase have dark brown fur.
Your friend has also made mice that are defective in the α subunit of the G protein
in this signaling pathway. The defective α subunit works normally except that,
once it binds GTP, it cannot hydrolyze GTP to GDP. What color do you predict
that the fur of these mice will be? Why?
16-54 Bacteria undergo chemotaxis toward amino acids, which usually indicates the
presence of a food source. Chemotaxis receptors bind a particular amino acid and
cause changes in the bacterial cell that induce the cell to move toward the source
of the amino acid. Four types of chemotaxis receptor that mediate responses to
different amino acids have been identified in a bacterium. The receptors are called
ChrA, ChrB, ChrC, and ChrD. Each receptor specifically senses serine, aspartate,
glutamate, or glycine, although you do not know which receptor senses which
amino acid. You have been given a wild-type bacterial strain that contains all four
receptors, as well as various mutant bacterial strains that are lacking one or more
of the receptors.
To figure out which receptor senses which amino acid, you conduct experiments
in which you fill a capillary tube with an amino acid to attract the bacteria, dip the
capillary tube into a solution containing bacteria, remove the capillary tube after 5
minutes, and count the number of bacteria in the capillary tube. Your results are
shown in Table Q16-54.
Table Q16-54 Chemotaxis in wild-type and mutant strains of bacteria
From these results, indicate which receptor is used for which amino acid.