Biol 3040 Exam 3 In-Class Clicker Questions and Review Materials

Nitric Oxide gas released by endothelial cells in the blood vessels diffuses to induce relaxation of adjacent smooth muscle cells. This is an example of___________ signaling.

A. Endocrine

B. Paracrine

C. Synaptic

D. Contact-dependent

B. Paracrine

Extracellular signals can bind to

cell surface receptors

intracellular receptors

both

both

Can the same signal molecule induce different responses in different target cells?

YES!

ie) acetylcholine response in diff tissues

During nervous-system development in Drosophila, the membrane-bound protein Delta acts as an inhibitory signal to prevent neighboring cells from developing into neuronal cells. Delta is involved in ______________ signaling.

A. Endocrine

B. Paracrine

C. Synaptic

D. Contact-dependent

D. Contact-dependent

If signaling molecules act on the same cells that release them, it is an example of _____________ signaling.

A. Endocrine

B. Autocrine

C. Synaptic

D. Contact-dependent

B. Autocrine

What are the three main classes of cell surface receptors?

1. Ion Channel Coupled Receptors

2. G Protein Coupled Receptors (GPCR)

3. Enzyme Coupled Receptors

How is the activity of monomeric GTP-binding proteins is controlled?

By

GEFS = Guanine nucleotide Exchange Factor- GEF exchanges GDP for GTP to activate GTPase - ON

and

GAPS = GTPase Activating Protein – Stimulate hydrolysis of GTP to form GDP to turn off GTPase - OFF

Monomeric GTPases are in "ON-State(active)" upon binding to:

A. GDP

B. GTP

C. ADP

D. ATP

B. GTP

What are the three types of intracellular signaling complexes activated by cell-surface receptors?

1. Performed signaling complex on a scaffold protein

2. Assembly of signaling complex on an activated receptor

3. Assembly of signaling complex on phophoinositide docking site

What are the different types of responses to a gradual increasing signal?

- all or none

- hyperbolic

- sigmodial

What do sigmodial responses do?

Sigmoidal responses ensure that cells only respond to an increase in signal molecules beyond background or cross a certain concentration threshold

Which of these occur more rapidly in response to a signal?

A- Changes in protein phosphorylation

B- Changes in mRNA synthesis

A- Changes in protein phosphorylation

How can cells adjust their sensitivity to a signal?

1. negative feedback

2. delayed feed forward

3. receptor inactivation

4. receptor sequestration

5. receptor destruction

In the following graphs, the cellular response, as measured in real time by the concentration of a certain active effector protein, is plotted over time for five cell types (A to D) that are treated with three different concentrations of a signal molecule

Which cell type shows fastest signal adaptation?

1 nM (dotted curve)

5 nM (gray curve)

25 nM (solid curve

C

In the following graphs, the cellular response, as measured in real time by the concentration of a certain active effector protein, is plotted over time for five cell types (A to D) that are treated with three different concentrations of a signal molecule

Which cell type shows a response to the highest persistence

1 nM (dotted curve)

5 nM (gray curve)

25 nM (solid curve

A

GPCR

G-protein coupled receptor

7 transmembrane proteins

Gs - Stimulatory G protein

activate adenylyl cyclase

Gi - Inhibitory G protein

Inhibit adenylyl cyclase

Which of these best describe the GPCRs?

A- All receptors of this class are polypeptides with seven transmembrane segments.

B- Alter the membrane potential directly by changing the permeability of the plasma membrane.

C- Must be coupled with intracellular monomeric GTP-binding proteins

A- All receptors of this class are polypeptides with seven transmembrane segments.

What does adrenaline do?

stimulates glycogen breakdown in skeletal muscle

The length of time a G protein will signal is determined by _______.

A- the activity of phosphatases that turn off G proteins by dephosphorylating Gα.

B- the activity of phosphatases that turn GTP into GDP.

C- the GTPase activity of Gα.

C- the GTPase activity of Gα.

Phosphatidyl Inositol

phosphatidate + inositol (derivative of glucose)

DAG (diacylglycerol

A second messenger produced by the cleavage of a PIP in the plasma membrane.

a secondary messenger that activates the enzyme protein kinase C and is involved in many signaling cascades

DAG ---> Protein Kinase C

adenyl cyclase

An enzyme that converts ATP to cyclic AMP in response to a chemical signal.

cAMP ---> Protein Kinase A

PIP

cleaved by phospholipase C into DAG and IP3

IP3

One of the products of PIP2 cleavage in the Ca++/phosphoinositide signal pathway.

Moves to cytoplasm to trigger Ca++ release from intracellular stores leading to Ca++/calmodulin cascade.

Mimicked by calcium ionophores (ionomycin)

What can nitric oxide do?

mediate signaling between cells

scaffold protein

improve the efficiency of a signaling cascade by holding all the participating enzymes in close proximity

organize groups of intracellular signaling molecules into signaling complexes

SH2

Src homology 2 domain

bind to phosphotyrosines

PTB

phosphotyrosine binding domain

SH3

binds proline rich amino acid sequences

PH

bind to charged head groups of phophoinositides

A GAP.......

stimulates the exchange of bound GDP for GTP.

enhances the GTP hydrolysis rate of monomeric GTPases.

inhibits the GTPase actvity of monomeric GTPase.

is a factor without which monomeric GTPases cannot hydrolyze GTP.

enhances the GTP hydrolysis rate of monomeric GTPases.

An extracellular signal that is in the vicinity of the cell that secretes it and thereby activates signaling in the surrounding cells is classified as:

paracrine signaling

endocrine signaling

autocrine signaling

synaptic signaling

paracrine signaling

Endocytosis of receptors followed by degradation in lysosomes in response to a signal is a mode of

receptor activation

positive feedback mechanism

receptor desensitization

receptor desensitization

Which of these domains bind to proline-rich sequences?

SH3 domain

PTB domain

PH domain

SH2 domain

SH3 domain

Which of these is not a type of Receptor?

Ligand-gated ion channels

GPCRs

Enzyme-coupled receptors

monomeric G proteins

monomeric G proteins

Which of these responses to a signal are likely to occur in seconds?

Translation

Transcription

Protein phosphorylation

Altered cell growth

Protein phosphorylation

Which of these statements is false?

Phosphatases catalytically remove the phosphate from GTP in GTP-binding proteins.

Serine-specific kinases or threonine-specific kinases are common types of protein kinases.

For activation of GTP-binding proteins, the GDP is exchanged for GTP.

Phosphatases catalytically remove the phosphate from GTP in GTP-binding proteins.

__________________ cells in select tissues release hormones that are distributed to the rest of the body.

Paracrine

Autocrine

Endocrine

Local Mediators

Endocrine

Among which of these signaling mechanisms (other than endocrine signaling) do signaling molecules move farthest away from the cells that release them?

Paracrine

Neuronal (synaptic)

Contact-dependent

Autocrine

Paracrine

Which of these are secreted extracellular signaling molecules that work only in the neighborhood they are released in?

Hormones

Local mediators

Receptors

Local mediators

Electrical impulses sent along a neuronal axon reaches the synapse and triggers secretion of a chemical called...........

Neurotransmitter

Nucleotides

Receptors

GTPases

Neurotransmitter

Charged phosphoinositides are recognized and bound by

SH2 domains

Pleckstrin Homology domain

SH3 domain

PTB domain

Pleckstrin Homology domain

Pleckstrin Homology domain

Protein domain found in intracellular signaling proteins by which they bind to inositol phospholipids phosphorylated by PI 3-kinase.

What's the name of the domain that PDK1 is using to bind to PIP3?

aa seq on certain proteins that allow binding to PI3,4,5,trisP and PI4,5bisP

Scaffold proteins affect amplification and speed of signal by..................

limiting amplification but improving speed.

enhancing amplification similar to diffusible messengers and enhacing speed.

limiting amplification and speed.

improving amplification similar to diffusible messengers but limiting speed.

limiting amplification but improving speed.

Src Homology Domains (SH2) bind to which of these residues on activated receptors?

Serine

Arginine

Phosphorylated Tyrosine

Ubiquitinated lysine

Phosphorylated Tyrosine

Activation of which of these proteins leads to the activation of a monomeric GTPase by releasing GDP and binding GTP.

Guanine nucleotide exchange factor (GEF)

GTPase-activating protein (GAP)

Scaffold protein

Adaptor

Guanine nucleotide exchange factor (GEF)

Which of these enzymes phosphorylate a protein by transferring the terminal phosphate from ATP onto a serine, threonine or tyrosine residue?

Kinase

Phosphatase

Monomeric GTPase

Ligase

Kinase

A signaling molecule can generate a strong signaling response that persists even after the signaling molecule is removed and this can be due to:

Positive feedback

Negative feedback

No feedback

Positive feedback

Amplification of response to a signal can be generated when receptor activation leads to generation of a large number of intracellular signaling molecules/chemicals called................

kinases.

first messengers.

intracellular receptors.

second messengers.

second messengers.

Family of G proteins

T he two monomers in a receptor tyrosine kinase dimer phosphorylate each other and the process is called..................

A- Nucelotide exchange

B- Ubiquitination

C- Serine Phosphorylation

D- Trans-autophosphorylation

D- Trans-autophosphorylation

What do the monomeric GTPase Ras superfamily do?

mediates signaling by most RTKs

Ras-GEF

Promotes exchange of GDP for GTP on Ras

Ras-GAP

promotes hydrolysis to inactive Ras

Can Ras activate a MAP kinase signaling molecule?

YES

How does Ras become oncogenic?

by activating mutations

Which of the following mechanisms is not directly involved in inactivating an activated RTK (Receptor Tyrosine Kinase)?

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

A- dephosphorylation by serine/threonine phosphatases

How do scaffold proteins help w MAP kinase modules?

they prevent cross talk between parallel MAP kinase modules

What is this molecule?

A- Phosphatidylinsoitol-3-phosphate

B- Inositol 1,4,5 triphosphate

C- Phosphatidylinsoitol- 4,5-bisphosphate

D- Phosphatidylinsoitol- 3, 4,5-triphosphate

B- Inositol 1,4,5 triphosphate

What signal molecules bind to intracellular receptors?

small hydrophobic signaling molecules

Activation of Notch is irreversible?

A) TRUE

B) FALSE

TRUE

this is because it gets cleaved and then later notch gets endocytosed in delta signal cell

α subunit of G-protein is bound to _____________, that is replaced with __________________ upon activation of GPCR.

ADP, ATP

ATP, ADP

GTP, GDP

GDP, GTP

GDP, GTP

Inactivation of the α subunit of a trimeric G protein in enhanced by .......

GEF activity of GPCR.

GAP activity of RGS.

GEF activity of RGS.

GAP activity of GPCR.

GAP activity of RGS.

cAMP is synthesized from ATP by............

cAMP phosphodiesterase

cGMP phosphodiesterase

GPCR

adenylyl cyclase

adenylyl cyclase

Response to a signal reaches a maximum level before it shuts itself off followed by another pulse of maximal response even in the presence of the signaling molecule leading to an oscillatory response due to............

negative feedback with a long delay

persisting positive feedback

lack of feedback

negative feedback with a long delay

PKA is activated by binding of cAMP to the .........

both regulatory and catalytic subunits

catalytic subunits

cAMP phosphodiesterase

regulatory subunits

regulatory subunits

Which type of mutation in the regulatory subunits of PKA would lead to a permanently inactive state?

Mutation in the regulatory subunits that prevents the release of the catalytic subunits.

Mutation in the cAMP binding site in the regulatory subunits that results in permanent binding of cAMP.

Mutation in the regulatory subunits that prevents them from binding to the catalytic subunits.

Mutation in the regulatory subunits that prevents the release of the catalytic subunits.

NO produced in endothelial cells diffuses across the membranes into smooth muscle cells to stimulate synthesis of cGMP by binding to.....

Adenylyl cyclase

cGMP phosphodiesterase

Guanylyl cyclase

protein kinase

Guanylyl cyclase

NOS catalyzed deamination of which of these amino acids produces NO?

Serine

Arginine

Threonine

Tyrosine

Arginine

Cholera toxin activates the alpha subunit of Gs by ADP ribosylation, which.........

inhibits the GTP hydrolysis activity of alpha subunit.

activates the GTP hydrolysis activity of alpha subunit.

inhibits adenylyl cyclase activity.

activates GDP binding to alpha subunit.

inhibits the GTP hydrolysis activity of alpha subunit.

Increase in cAMP levels by extracellular signals can be balanced by breakdown of cAMP by enzyme.........

adenylyl cyclase

guanylyl cyclase

cAMP phosphodiesterase

protein kinase

cAMP phosphodiesterase

Activation of phospholipase C by G protein leads to .......

inhibition of PKC.

cleavage of inositol phospholipids.

inhibition of calcium release from ER.

cleavage of inositol phospholipids.

Exposure of target cells to prolonged signals can lead to desensitization of GPCR by...................

binding of arrestin to phosphorylated GPCR.

dephosphorylation of GPCR.

continued interaction with G protein.

binding of arrestin to phosphorylated GPCR.

IP3 produced by phospholipase C activation binds to IP3 receptors and leads to .......

a rise in magnesium levels.

a drop in cytosolic calcium levels.

an inhibition of calcium release from ER.

release of calcium from ER into cytosol.

release of calcium from ER into cytosol.

Which of these statements about nuclear receptors are true?

They only enter the nucleus after binding to ligand.

They always activate transcription upon binding to ligands in the nucleus.

They can activate or repress transcription based on the type of receptor.

They can activate or repress transcription based on the type of receptor.

PI 3-kinase ......

activates PDK1 by phosphorylating a serine residue on the protein.

is counteracted by PTEN phosphatase.

is only known to be activated by receptor tyrosine kinases.

removes phosphate groups from Serine or Threonine residues.

is counteracted by PTEN phosphatase.

Which of these do not describe Notch?

It is a cell-surface receptor.

Notch tail is released to activate translation.

It is activated by proteolytic processing that involves a series of cleavage steps.

Notch tail is released to activate translation.

Mutations that disrupt the protease activity of gamma-secretase will...................

inhibit recognition of Notch by Delta.

activate transcription of Notch target genes.

inhibit transcription of Notch target genes.

activate migration of Notch into nucleus.

inhibit transcription of Notch target genes.

Mutations in the SH2 domains of the Grb2 adaptor that inhibit recognition of RTKs will lead to.....................

activation of Sos -GEF.

inhibition of GTP binding to Ras.

exchange of GDP for GTP in Ras.

inhibition of GTP binding to Ras.

Activation of the EGF receptor includes which of these mechanisms?

Phosphorylation by the activator and the receiver.

Conformational change in the receiver.

Phosphorylation of both the monmers by only the activator.

Momomerization of the receptors upon binding to EGF.

Conformational change in the receiver.

In reference to AKT-dependent regulation of Bad, select the statement that is false?

In the absence of a survival signal, Bad is phosphorylated.

In the absence of a survival signal, Bad inhibits the cell-death inhibitor protein Bcl2.

In the presence of a survival signal, Akt is phosphorylated.

In the presence of a survival signal, the cell-death inhibitory protein Bcl2 is active.

In the absence of a survival signal, Bad is phosphorylated.

AKT and ERK activate mTORC1 activity by directly phosphorylating and inhibiting which of these GAPs?

RGS

Gator1

Ras GAPs

TSC

TSC

Upon activation of Ras, the final kinase activated in the MAP Kinase module is...........

Mek

Erk

Raf

MAPKKK

Erk

What of these statements about mTORC1 or mTORC2 are true?

mTORC2 is sensitive to drug rapamycin.

mTORC1 complex activates AKT directly.

mTORC1 is sensitive to rapamycin.

mTORC2 activity is dependent on Rag,

mTORC1 is sensitive to rapamycin.

The GEF that activates Rag GTPase is..............

Gator1

mTORC1

Rheb

Ragulator

Ragulator

Mutations that inhibit TSC activity leads to the disease- Tuberous Sclerosis that has benign tumors and giant cells and this is due..............

high mTORC1 activity.

inhibition of mTORC1 activity.

inhibition of AKT.

increased Rheb GTPase activity.

high mTORC1 activity.

Enhancement of Gator1 GAP activity will lead to.................

inhibition of mTORC1 activity.

activation of mTORC1 activity.

inhibition of mTORC2 activity.

activation of mTORC2 activity.

inhibition of mTORC1 activity.

In the absence of a Wnt signal.............

Beta-catenin is stabilized.

Beta-catenin is degraded.

Beta-catenin accumulates and translocates to nucleus.

LEF1/TCF transcription regulator is activated.

Beta-catenin is degraded.

Degradation of Beta-Catenin by the proteasome is stimulated by..................

disassembly of the APC/Axin degradation complex.

phosphorylation of Beta-Catenin by GSK3 and CK1.

dephosphorylation of Beta-Catenin.

inhibition of GSK3 and CK1 kinases.

phosphorylation of Beta-Catenin by GSK3 and CK1.

Which of these events are likely to occur if Beta-Catenin is unable to bind to LEF1/TCF in the presence of Wnt signal?

Wnt target genes will be turned ON constitutively.

LEF1/TCF will activate the transcription of Wnt target genes.

Groucho will remain bound to LEF1/TCF.

Groucho will be displaced from LEF1/TCF.

Groucho will remain bound to LEF1/TCF.

A receptor tyrosine kinase-A (RTK-A) is activated by binding to a growth factor (GF). Which type of mutation is likely to inhibit the dimerization of RTK.

a mutation that increases the affinity of RTK-A for GF

a mutation that prevents RTK-A from binding to GF

mutation of tyrosines in RTK that inhibit trans-autophosphorylation.

mutation in the SH2 domain of intracellular signaling factor that recognizes phosphotyrosines in RTK.

a mutation that prevents RTK-A from binding to GF

Akt

A serine/threonine kinase that is activated by PIP3 and plays a key role in signaling cell survival.

Why is Wnt/Beta-Catenin signaling important?

It allows for cells to be made in the stem cell stage and cell profileration

APC and Axin

form a complex through a scaffold protein

frizzled

receptor in the Wnt pathway - Wnt signal binds to this

NOT A GPCR

Groucho

Inhibits LEF1/TCF - displaced by beta-catenin

There is no fundamental chemical distinction between signaling molecules that bind to cell-surface receptors and those that bind to intracellular receptors.

A. True

B. False

B. False

they do have diff chemical distinction as intracellular signals need to be hydrophobic or polar

W hat is the term for the protein that organizes groups of interacting intracellular signaling proteins into signaling complexes?

A. Intracellular receptor

B. Kinase cascade

C. Scaffold protein

D. Interaction domain

C. Scaffold protein