Chapter 16 - Cell Signaling

Question 1

When cells respond to an extracellular signal, they most often convert the information carried by this molecule from one form to another. What is this process called?

• signal transduction
• signal detection
• signal integration
• signal amplification
• signal production

Answer 1

Signal transduction

(Signal transduction begins when the receptor on a target cell receives an incoming extracellular signal and then produces intracellular signaling molecules that alter cell behavior.)

Question 2

Many of the extracellular signal molecules that regulate inflammation are released locally at the site of infection. What form of cell–cell signaling is being used?

• paracrine
• endocrine
• contact-dependent
• neuronal

Answer 2

Paracrine

(In paracrine signaling, the extracellular signaling molecule acts as a local mediator on cells located nearby the signaling cell that produced it.)

Question 3

Which statement about cell signaling is correct?

• All extracellular signal molecules act by binding to receptors on the cell surface.
• All cell types are able to respond to the same set of signal molecules.
• Each receptor triggers one particular type of cell behavior, for example, activating gene expression.
• Each receptor is generally activated by only one type of signal molecule.
• Each type of extracellular signal molecule induces the same response in all target cells.

Answer 3

Each receptor is generally activated by only one type of signal molecule.

(Small molecules like acetylcholine, for example, usually bind to a pocket formed by amino acids from several transmembrane segments of the receptor. These amino acids form noncovalent interactions with the signal molecule, allowing the receptor to recognize and bind specifically to its signal.)

Question 4

Which statement about positive feedback regulation is accurate?

• In positive feedback, a downstream component acts to inhibit an earlier component in the pathway to diminish the response to the initial signal.
• Positive feedback can generate responses that oscillate on and off as the activities or concentrations of the participating components rise and fall.
• Positive feedback is rare in biological systems.
• Positive feedback regulation can generate an abrupt, all-or-none response in which the cell moves from ignoring a signal to responding to it very strongly.
• In positive feedback, a molecular switch enhances the response to a signal by activating a component that lies downstream in the pathway.

Answer 4

Positive feedback regulation can generate an abrupt, all-or-none response in which the cell moves from ignoring a signal to responding to it very strongly.

(In some cases, such a response can be self-sustaining and will persist even after the signal is no longer present.)

Question 5

What is true of the GTP-binding proteins that act as molecular switches inside cells?

• They turn themselves on by hydrolyzing GTP to form GDP.
• They are active when GTP is bound.
• They are active when GDP is bound.
• They turn themselves on by phosphorylating GDP to form GTP.
• They are active only in their trimeric forms.

Answer 5

They are active when GTP is bound.

(Once activated by GTP binding, many of these proteins have intrinsic GTP-hydrolyzing (GTPase) activity, and they shut themselves off by hydrolyzing their bound GTP to GDP.)

Question 6

Which is true of the GTP-binding proteins that participate in intracellular signaling?

• Only trimeric GTP-binding proteins relay messages from G-protein-coupled receptors.
• Only trimeric GTP-binding proteins interact with guanine nucleotide exchange factors (GEFs).
• Only monomeric GTP-binding proteins relay messages from G-protein-coupled receptors.
• Only trimeric GTP-binding proteins participate in intracellular cell signaling.
• G-protein-coupled receptors interact with all types of GTP-binding proteins.

Answer 6

Only trimeric GTP-binding proteins relay messages from G-protein-coupled receptors.

(There are several varieties of G proteins. Each is specific for a particular set of receptors and for a particular set of target enzymes or ion channels in the plasma membrane.)

Question 7

What is true of ion-channel-coupled receptors?

• They transduce signals in a simple and direct manner.
• They are voltage-gated.
• They transduce signals via elaborate intracellular signaling pathways.
• They are found only in nerve cells.
• They integrate multiple signals at the same time.

Answer 7

They transduce signals in a simple and direct manner.

(Ion-channel-coupled receptors do not activate the sort of elaborate intracellular signaling pathways used by G-protein-coupled receptors or enzyme-coupled receptors.)

Question 8

Why does nitric oxide (NO) act as a paracrine signal that affects only neighboring cells?

• It is rapidly converted to nitrates and nitrites in the target cell.
• Cell-surface NO receptors are expressed only on cells in close proximity to NO signaling cells.
• It is rapidly washed away by the bloodstream.
• It is rapidly converted to nitrates and nitrites in the extracellular fluid.
• It diffuses rapidly into the atmosphere.

Answer 8

It is rapidly converted to nitrates and nitrites in the extracellular fluid.

(Reaction with oxygen and water in the extracellular environment converts NO into nitrates and nitrites within seconds of its release by the cells that produce it.)

Question 9

Signaling via a GPCR ceases when which condition occurs?

• The G protein associates with an activated GPCR.
• The G protein dissociates from the activated GPCR.
• The α subunit hydrolyzes its bound GTP.
• The α subunit exchanges GDP for GTP.
• The α subunit dissociates from the βγ complex.

Answer 9

The α subunit hydrolyzes its bound GTP.

(GTP hydrolysis and inactivation usually occur within seconds after the G protein has been activated. The inactive G protein is then ready to be reactivated by another activated receptor.)

Question 10

Which response to GPCR stimulation would be most rapid?

• activation of a G protein that inhibits adenylyl cyclase
• change in the activation of a set of target genes
• activation of a G protein that activates adenylyl cyclase
• activation of a G protein that activates phospholipase C
• activation of a G protein that regulates the opening of an ion channel

Answer 10

activation of a G protein that regulates the opening of an ion channel

(When G proteins interact with ion channels, they cause an immediate change in the state and behavior of the cell.)

Question 11

When activated phospholipase C cleaves an inositol phospholipid, what happens to the small signaling molecules the enzyme produces?

• Both inositol 1,4,5-trisphosphate (IP3) and Ca2+ are released into the cytosol.
• Inositol 1,4,5-trisphosphate (IP3) is released into the cytosol, while diacylglycerol is retained in the membrane.
• Inositol 1,4,5-trisphosphate (IP3) remains in the membrane, while diacylglycerol is released into the cytosol.
• Both inositol 1,4,5-trisphosphate (IP3) and diacylglycerol are retained in the membrane.
• Both inositol 1,4,5-trisphosphate (IP3) and diacylglycerol are released into the cytosol.

Answer 11

Inositol 1,4,5-trisphosphate (IP3) is released into the cytosol, while diacylglycerol is retained in the membrane.

(IP3 binds to and opens Ca2+ channels that are embedded in the endoplasmic reticulum (ER) membrane; diacylglycerol remains in the membrane, where it helps to recruit and activate protein kinase C (PKC).)

Question 12

What are small intracellular signaling molecules often called?

• first messengers
• transmitter-gated ion channels
• second messengers
• intracellular signaling proteins
• extracellular signaling molecules

Answer 12

Second messengers

(The “first messengers” are the extracellular signals that activate the enzymes that produce the second messengers. These second messengers rapidly diffuse from their site of synthesis and thereby amplify and spread the intracellular signal.)

Question 13

Because cyclic AMP diffuses quickly through the cytosol and a cyclic AMP phosphodiesterase rapidly converts cyclic AMP to AMP, what is the consequence?

• The cytosolic concentration of cyclic AMP can change rapidly.
• The responses triggered by an increase in cyclic AMP are slow.
• The responses triggered by an increase in cyclic AMP are rapid.
• Cells must sequester cyclic AMP.
• Cyclic AMP is not often used to mediate cell responses.

Answer 13

The cytosolic concentration of cyclic AMP can change rapidly.

(The rapid synthesis, diffusion, and elimination of cAMP allows the concentration of this second messenger to rise or fall tenfold in a matter of seconds.)

Question 14

What do the phosphorylated tyrosines on activated RTKs do?

• They serve as binding sites for a variety of intracellular signaling proteins.
• They promote receptor internalization.
• They serve as binding sites for G proteins.
• They help the receptor dimerize.
• They activate the enzymatic activity of the RTKs.

Answer 14

They serve as binding sites for a variety of intracellular signaling proteins.

(Some of these proteins become phosphorylated and activated on binding to the receptors, and they then propagate the signal; others function solely as scaffolds, which couple the receptors to other signaling proteins, thereby helping to build the active signaling complex.)

Question 15

Ras is activated by a Ras-activating protein that does what?

• causes Ras to hydrolyze its bound GTP
• causes Ras to exchange GDP for GTP
• causes Ras to interact with a phosphorylated RTK
• dephosphorylates Ras
• phosphorylates Ras

Answer 15

causes Ras to exchange GDP for GTP

(An adaptor protein, docked on a particular phosphotyrosine on the activated receptor, recruits the Ras guanine nucleotide exchange factor (Ras‑GEF), which stimulates Ras to exchange its bound GDP for GTP.)

Question 16

RTKs can activate the enzyme phosphoinositide 3-kinase, which phosphorylates inositol phospholipids. These phospholipids then do what?

• activate Ras
• activate G proteins
• serve as docking sites that recruit specific intracellular signaling proteins to the plasma membrane
• serve as phosphate donors in phosphorylation reactions
• activate Ca2+ channels in the plasma membrane, promoting an influx of Ca2+ into the cytosol

Answer 16

Serve as docking sites that recruit specific intracellular signaling proteins to the plasma membrane

(One of the most important of these recruited proteins is a kinase called Akt.)

Question 17

PI 3-kinase acts by phosphorylating what molecule(s)?

• serines or threonines on protein kinases that phosphorylate Akt
• tyrosines on protein kinases that phosphorylate Akt
• tyrosines of Akt
• inositol phospholipids
• serines or threonines of Akt

Answer 17

Inositol phospholipids

(These phosphorylated lipids serve as docking sites for other intracellular signaling proteins, which then activate one another.)

Question 18

Ethylene is a hormone that promotes the ripening of fruit. What happens in the absence of ethylene?

• The activated ethylene receptor promotes the degradation of a transcription regulator and the ethylene-responsive genes remain turned off.
• The ethylene receptor is internalized and degraded, shutting down the expression of the ethylene-responsive genes.
• The ethylene receptor is inactive and the transcription regulator needed to turn on the ethylene-responsive genes is degraded.
• The ethylene receptor is inactive and a transcription regulator shuts off the ethylene-responsive genes.
• The activated ethylene receptor switches on a transcription regulator that inhibits the expression of ethylene-responsive genes.

Answer 18

The activated ethylene receptor promotes the degradation of a transcription regulator and the ethylene-responsive genes remain turned off.

(In the absence of ethylene, the receptor directly activates an associated protein kinase, which then indirectly promotes the destruction of the transcription regulator that switches on ethylene-responsive genes. As a result, the genes remain turned off.)

Question 19

Ras can exist in two different conformations or states, inactive and active. Which of the following correctly describe(s) the stably active state of Ras?
Choose one or more:

• Ras is bound to GTP.
• Ras is bound to GDP.
• Ras is bound to Ras-GAP.
• Switch 1 and switch 2 regions are in an active conformation.

Answer 19

• Ras is bound to GTP.
• Switch 1 and switch 2 regions are in an active conformation.

(Binding to GTP changes the switch 1 and switch 2 regions to the active conformation, leading to activation of the Ras protein.)

Question 20

Specific amino acids, including Arg 789 in Ras-GAP and amino acids Gln 61 and Thr 35 in Ras, all play an important role in Ras function. Why are these amino acids important?

• They help Ras bind GDP tightly.
• They help Ras bind GTP tightly.
• They help facilitate GTP hydrolysis by Ras.
• They help downstream signaling by binding to additional signaling proteins.

Answer 20

They help facilitate GTP hydrolysis by Ras.

The amino acids in Ras-GAP and Ras hydrolyze the bound GTP, inactivating Ras.

Question 21

Which of these represents a mechanism used to terminate a signal transmitted by activated RTKs?

• SH2 domains are internalized and digested in lysosomes.
• The RTKs are internalized and digested in lysosomes.
• SH2 domains remove the phosphates from RTKs and other intracellular signaling proteins.
• Tyrosine kinases remove the phosphates from RTKs and other intracellular signaling proteins.
• The RTK is inactivated by phospholipase C.

Answer 21

The RTKs are internalized and digested in lysosomes.

(Activated receptors can also be switched off in a more readily reversible manner, by removal of their activating phosphates by a tyrosine phosphorylase.)

Question 22

What makes it possible for a combination of signal molecules to evoke a response that differs from the sum of the effects that each signal could trigger on its own?

• the ability of different receptors to activate different intracellular relay systems
• the ability of the same signal molecule to bind to different receptors
• the ability of different signal molecules to bind to the same receptor
• the ability of different intracellular relay systems to interact
• the tendency of different cells to display different receptors

Answer 22

The ability of different intracellular relay systems to interact

(A cell can integrate and tailor its response to a combination of signals in part because the intracellular relay systems activated by the different signals interact. Thus, the presence of one signal will often modify the effects of another.)

Question 23

Which of the following signaling pathways would be likely to trigger the most rapid cell response?

• Adrenaline binds to a GPCR to activate a cyclic AMP signaling pathway that triggers glycogen breakdown.
• Acetylcholine binds to anion-channel-coupled receptor that allows Na+ to flow down its electrochemical gradient, triggering contraction of a skeletal muscle cell.
• Adrenaline binds to a GPCR to activate a cyclic AMP signaling pathway that triggers the synthesis of hormones in endocrine cells.
• Platelet-derived growth factor binds to a receptor tyrosine kinase to activate a signaling pathway that stimulates cell proliferation at the site of a wound.
• Nerve growth factor binds to a receptor tyrosine kinase to activate a signaling pathway that enhances the transcription of Bcl2, a protein that suppresses cell death.

Answer 23

Acetylcholine binds to anion-channel-coupled receptor that allows Na+ to flow down its electrochemical gradient, triggering contraction of a skeletal muscle cell.

(Ion-channel-coupled receptors are the simplest and most direct cell-surface receptors. Activation of an ion-channel-coupled receptor can trigger a response in milliseconds—thousands of a second.)

Question 24

In skeletal muscle cells, epinephrine (adrenaline) stimulates the breakdown of glycogen by activating a GPCR. In the signaling pathway shown here, which step does not amplify the original signal?

• activation of glycogen phosphorylase by activated phosphorylase kinase
• activation of adenylyl cyclase by an activated G protein
• activation of phosphorylase kinase by activated PKA
• activation of a G protein by an activated GPCR
• production of cyclic AMP by activated adenylyl cyclase

Answer 24

activation of adenylyl cyclase by an activated G protein

(Adenylyl cyclase is activated by the binding of an activated α subunit of the G protein Gs. When the α subunit hydrolyzes its bound GTP, it will dissociate from adenylyl cyclase, rendering the enzyme inactive once again.)

Question 25

True or False

The initial rise in protein X activity is due to the direct and rapid activation by the kinase. The activity begins to fall as the kinase activates the phosphatase, which slowly inactivates protein X.

Answer 25

True

(Investigators are studying a pathway in which an intracellular signaling protein, X, is activated by phosphorylation of a specific tyrosine. The binding of the extracellular signal molecule to its cell-surface receptor activates a kinase that rapidly phosphorylates this tyrosine.

The same kinase, however, also activates a phosphatase that removes the phosphate group from protein X. This phosphatase operates more slowly than the kinase.

In the graph, the extracellular signal is present during the period shown in gray. The dashed line represents the response of protein X when the phosphatase has not been activated by the protein kinase.)

Question 26

Which of the following steps are required in the activation of the G-protein signaling pathway?
Choose one or more:

• Ligand binds to the G-protein-coupled receptor.
• Gα exchanges GDP for GTP.
• The activated receptor induces interaction between Gα and Gβγ.
• Activated Gα influences target proteins.

Answer 26

• Ligand binds to the G-protein-coupled receptor.
• Gα exchanges GDP for GTP.
• Activated Gα influences target proteins.

(Activated receptor causes Gα and Gβγ to dissociate.)

Question 27

Alterations in signaling in the pituitary gland can lead to …

Answer 27

human disease

Question 28

The GH-releasing hormone (GHRH) stimulates _________ from the pituitary gland by binding to GHRH receptors, which are G-protein-coupled receptors.

Answer 28

release of growth hormone (GH)

Question 29

Excessive activity of the GHRH signaling pathway leads to ________, which can lead to acromegaly, a form of gigantism.

Answer 29

excessive release of growth hormone

Some patients can reach more than 8 feet tall as they continue to grow even in adulthood.

Question 30

Consider steps that could be taken to reduce GH release. What intervention methods would decrease GH?

Answer 30

• Inhibit interaction of G-alpha with receptor
• Block ligand binding to receptor
• Activate phosphorylation of the receptor by GRK kinase

(Decreasing signaling by the GHRH pathway would reduce GH release and could help the patients. Blocking binding of the receptor to ligand and Gα would reduce pathway activation, as would phosphorylation of the receptor by GRK.)

Question 31

Consider steps that could be taken to reduce GH release. What intervention methods would increase GH release?

Answer 31

• Block binding of arrestin to the receptor

- Block hydrolysis of GTP

Question 32

What is required for PKC activation?

• binding to DAG
• binding to DAG and continuing presence of Ca2+
• binding to Gq
• continuing presence of Ca2+
• binding to Gq and DAG

Answer 32

binding to DAG and continuing presence of Ca2+

Activation of PKC occurs through binding to DAG and the continuing presence of Ca2+.

Question 33

IP3 signaling helps regulate sweating, which is important for regulating body temperature. Anhidrosis, the inability to sweat normally, can be caused by genetic and environmental factors. A rare mutation has been identified in a family with several children suffering from anhidrosis. The mutation inactivates the protein that IP3 binds on the ER membrane. Suppose cells were isolated from affected family members and exposed to different treatments. Which of the following treatments would be able to repair the signaling defect in cells isolated from these patients?

• activation of phospholipase Cβ in the cell
• addition of high amounts of Ca2+ in the cytosol
• addition of high amounts of IP3 in the cell
• addition of PKC to the cell

Answer 33

addition of high amounts of Ca2+ in the cytosol

Adding high levels of Ca2+ to the cytosol will restore signaling and activation of PKC.

Question 34

Serotonin (5-hydroxytryptamine, 5-HT) is a neurotransmitter with receptors (5-HT receptors) located in cells throughout the body. There are more than a dozen different types of serotonin receptors that fall into several different classes. One class consists of serotonin-activated ion channels and the other receptor classes are G-protein-coupled receptors that associate with different G proteins. The 5-HT7A receptor couples to Gs and activates adenylyl cyclase, while the 5-HT2B receptor couples to Gq and activates phospholipase C. The diversity of receptor types has led pharmacologists to search for drugs that will bind to and modulate just a single receptor class in order to limit systemic side effects (see 5-Hydroxytryptamine Receptor Subtypes and their Modulators with Therapeutic Potentials)

What are the downstream effects predicted for a drug that exclusively activates the 5-HT7A receptor?

Answer 34

• cAMP production

- PKA activation

Question 35

Serotonin (5-hydroxytryptamine, 5-HT) is a neurotransmitter with receptors (5-HT receptors) located in cells throughout the body. There are more than a dozen different types of serotonin receptors that fall into several different classes. One class consists of serotonin-activated ion channels and the other receptor classes are G-protein-coupled receptors that associate with different G proteins. The 5-HT7A receptor couples to Gs and activates adenylyl cyclase, while the 5-HT2B receptor couples to Gq and activates phospholipase C. The diversity of receptor types has led pharmacologists to search for drugs that will bind to and modulate just a single receptor class in order to limit systemic side effects (see 5-Hydroxytryptamine Receptor Subtypes and their Modulators with Therapeutic Potentials)

What are the downstream effects predicted for a drug that exclusively activates the 5-HT2B receptor?

Answer 35

• Cytosolic calcium increase
• PKC activation
• IP3 production

(Adenylyl cyclase converts ATP into cAMP, activating cAMP-dependent protein kinase (PKA). Phospholipase C cleaves an inositol phospholipid into diacylglycerol and IP3. IP3 opens calcium channels, increasing cytosolic calcium levels. The increased calcium, along with diacylglycerol, activates PKC.)

Question 36

The drug Viagra promotes blood vessel dilation by prolonging signaling through nitric oxide (NO). How does Viagra boost NO?

• It prevents acetylcholine from binding to its receptors.
• It stimulates guanylyl cyclase in smooth muscle cells.
• It inhibits guanylyl cyclase in smooth muscle cells.
• It blocks the enzyme that degrades cyclic GMP.
• It binds to acetylcholine receptors on endothelial cells.

Answer 36

It blocks the enzyme that degrades cyclic GMP.

(NO produces penile erection by activating guanylyl cyclase and stimulating the formation of cyclic GMP; drugs like Viagra inhibit the phosphodiesterase that breaks down cyclic GMP, thus prolonging the activating effects of NO.)

Question 37

Which statement about signaling through GPCRs is correct?

• The signal molecules that bind to GPCRs all have a similar structure.
• Signaling cascades associated with GPCRs always operate at the same speed, regardless of the initiating signal.
• Some G proteins inhibit the production of cyclic AMP.
• All second messenger molecules diffuse rapidly through the cytosol, thereby amplifying and spreading the signal.
• The cyclic AMP pathway can activate gene transcription, whereas the inositol phospholipid pathway cannot.

Answer 37

Some G proteins inhibit the production of cyclic AMP.

(Not all G proteins that interact with adenylyl cyclase stimulate cyclic AMP production. The G protein Gi inhibits adenylyl cyclase.)

Question 38

Investigators are studying a signaling pathway in which an RTK activates the monomeric GTPase Ras. They discover that two new proteins, A and B, have a role in this signaling pathway: cells in which either of these proteins is disabled by mutation no longer show a response to the signal molecule that binds to the RTK.

To determine the order in which these proteins act, investigators introduce a continuously active form of Ras into each mutant cell line and record whether this treatment restores signaling.

Based on the results shown above, which of the following best represents the signaling pathway under investigation?

• RTK → Protein A → Protein B → Ras → → cell response
• RTK → Ras → Protein A → Protein B → → cell response
• RTK → Protein B → Ras → Protein A → → cell response
• The results are insufficient to make any prediction about the order in which the proteins act in the signaling pathway.
• RTK → Protein A → Ras → Protein B → → cell response

Answer 38

RTK → Ras → Protein A → Protein B → → cell response

(Because Ras acts downstream of protein B, constitutively active Ras will restore signaling to cells in which B is disabled by mutation. This “rescue” will occur even in the absence of the signal molecule that activates the pathway.)

Question 39

The signaling pathways shown below integrate information provided by signal 1 and signal 2 to activate the transcription of a target gene and trigger a cell response. The intracellular signaling molecules in the pathway are only active when they receive an activating signal (→) from an upstream signaling molecule and are not being inhibited (—I) by any upstream signaling molecule.

Given this information, under what conditions will the target gene for this signaling network be expressed?

• The target gene will be expressed only when signal 1 is present.
• The target gene will be expressed only when both signals are present.
• The target gene will be expressed only when signal 2 is present.
• The target gene will be expressed only when both signals are absent.
• The target gene will be expressed when either signal is present on its own.

Answer 39

The target gene will be expressed when either signal is present on its own.

(Each of the signals inhibits the signaling pathway of the other. Thus, the target gene will be expressed only when one of the signals is present and the other is absent.)

Question 40

A subset of breast cancers overexpress the receptor tyrosine kinase (RTK), known as human epidermal growth factor receptor 2 (HER2). Patients with HER2-positive breast cancers often benefit from treatment with a HER2-binding antibody known as Pertuzumab. Given that antibodies are large proteins that cannot cross the cell membrane, what might be directly impacted by Pertuzumab to limit cell proliferation?

• Pertuzumab prevents changes in gene expression by preventing transcription factor phosphorylation.
• Pertuzumab prevents receptor dimerization.
• Pertuzumab prevents adaptor protein binding to activated receptors.
• Pertuzumab prevents receptor coupling to G proteins.

Answer 40

Pertuzumab prevents receptor dimerization.

(RTKs require dimerization for activity. By binding to the extracellular part of the receptor, the bulky antibody prevents receptor dimerization and prevents downstream signaling.)

Question 41

The activity of a kinase called Src is regulated by phosphorylation. The kinase is inactivated by phosphorylation at a C-terminal tyrosine residue (Tyr527) and is activated by interaction with an activated RTK, which stimulates Src to autophosphorylate a different tyrosine residue (Tyr416). Full activation of Src requires removal of the inhibitory phosphate group and binding to an activated RTK.

Based on this information, which statement about the activity of Src kinase is correct?

• The kinase is active only when Tyr527 is phosphorylated and Tyr416 is dephosphorylated.
• The kinase is active only when Tyr527 is phosphorylated.
• The kinase is active only when Tyr416 is phosphorylated.
• The kinase is active only when Tyr416 is dephosphorylated.
• The kinase is active only when Tyr527 is dephosphorylated.
• The kinase is active only when Tyr527 is dephosphorylated and Tyr416 is phosphorylated.

Answer 41

The kinase is active only when Tyr527 is dephosphorylated and Tyr416 is phosphorylated.

(The dephosphorylation of the Tyr527 induces structural changes that open up the protein’s kinase domains, allowing the autophosphorylation of Tyr416.)

Question 42

Upon binding to an extracellular signal, a pair of RTKs dimerize and phosphorylate three tyrosine residues on each other’s cytoplasmic tails. These tyrosines serve as docking sites for three intracellular signaling proteins: phosphoinositide 3-kinase (PI 3-K), protein kinase X (PKX), and an adaptor protein (adaptor 1).

To determine which tyrosine is recognized by which downstream signaling protein, investigators construct a series of mutant receptor proteins in which the tyrosine residues are replaced, one at a time, with an alanine residue, preventing phosphorylation at that site. The signaling proteins recognized by each of these mutants are identified by co-immunoprecipitation and the effect that the mutations have on the cell’s response to the signal is recorded.

Based on the data, what can be concluded about this system?

• Phosphorylated tyrosine 3 serves as a docking site for PKX and PI 3-K.
• Adaptor 1 lacks an SH2 domain.
• Adaptor 1 binds to phosphorylated tyrosine 2.
• Phosphorylated tyrosine 2 serves as a docking site for PKX.
• PI 3-K can bind to phosphorylated tyrosines 2 or 3.
• PI 3-K is required for the normal cell response.

Answer 42

Phosphorylated tyrosine 2 serves as a docking site for PKX.

(When tyrosine 2 is changed to an alanine, PKX no longer recognizes the activated receptor complex and the signaling response is eliminated.)