MCB II UNIT 3 content, clickers, assignments

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) neuronal

(d) contact-dependent

contact dependent

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

Autocrine

What are the three main classes of cell-surface receptors?

Ion-Channel coupled receptors, G protein coupled receptors, and enzyme coupled receptors

G protein is a __________________ protein with ______, ________, and ________ subunits all found on the ______ side of the plasma membrane.

trimeric, alpha, beta, gamma, cytosolic

___________ receptors can have enzymatic activity of their or have an associated enzyme

enzyme-coupled

GEF exchanges ____ for _____

GDP for GTP in order to activate the GTPase

GAP exchanges _____ for ______

GTP for GDP through hydrolysis in order to turn off the the GTPase. You lose a phosphate in hydrolysis

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

A) GTP

B) GDP

C) ADP

D) ATP

GTP

True or false amplification is limited in a scaffolding protein

True they aren't amplifying anything, just turning things on

Which response is 1 receptor to 1 signaling molecule?

a) all or none

b) sigmoidal

c) hyperbolic

hyperbolic

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

A GAP.......

a) stimulates the exchange of bound GDP for GTP.

b) enhances the GTP hydrolysis rate of monomeric GTPases.

c) inhibits the GTPase actvity of monomeric GTPase.

d) is a factor without which monomeric GTPases cannot hydrolyze GTP.

b) 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:

a) paracrine signaling

b) endocrine signaling

c) autocrine signaling

d) synaptic signaling

a) paracrine signaling

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

a) receptor activation

b) positive feedback mechanism

c) receptor desensitization

c) receptor desensitization

Which of these domains bind to proline-rich sequences?

a) SH3 domain

b) PTB domain

c) PH domain

d) SH2 domain

a) SH3 domain

Which of these is not. a type of receptor?

a) ligand-gated ion channels

b) GPCRs

c) enzyme-coupled receptors

d) monomeric G proteins

d) monomeric G proteins

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

a) translation

b) transcription

c) protein phosphorylation

d) altered cell growth

c) protein phosphorylation

Which of these statements is false?

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

b) serine-specific kinases or threonine-specific kinases are common types of protein kinases

c) 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.

a) paracrine

b) autocrine

c) endocrine

d) 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?

a) paracrine

b) neuronal (synaptic)

c) contact-dependent

d) autocrine

paracrine, but if endocrine were on here it would be that. BE CAREFUl

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

a) Hormones

b) Local mediators

c) Receptors

b) Local mediators

Charged phosphoinositides are recognized and bound by

a) SH2 domains

b) Pleckstrin Homology domain

c) SH3 domain

d) PTB domain

b) Pleckstrin Homology domain

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

a) limiting amplification but improving speed.

b) enhancing amplification similar to diffusible messengers and enhacing speed.

c) limiting amplification and speed.

d) improving amplification similar to diffusible messengers but limiting speed.

a) 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.

a) Guanine nucleotide exchange factor (GEF)

b) GTPase-activating protein (GAP)

c) Scaffold protein

d) Adaptor

a) 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:

a) positive feedback

b) negative feedback

c) 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

in a g protein ___ and ___ subunits are membrane bound

alpha and gamma

Which G-protein subunit binds GDP?

alpha subunit has the gtpase

G protein's alpha subunit has two domains. What are they?

Ras domain and Alpha helical (AH) domain. Alpha helical domain will keep the GTP in but it can be opened when GPCR receives a signal and causes a conformational change

Does GPCR behave more like GEF or GAP?

GEF, because it helps activate the G protein by helping it exchange GDP for GTP with a conformational change.

After the alpha subunit of the G protein gets activated, it separates from the beta and gamma subunits. True or False

True, and the beta and gamma subunits are still on even though they are separated from the alpha subunit

G proteins activate enzymes that increase the concentrations of _______

second messenger molecules (cAMP, Ca2+)

Which of these best describes all 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

GPCR will activate a G protein to activate the enzyme (1)___________, which will help make (2)________, which can then activate (3)________. (3) will then enter the nucleus through a pore and activate (4) _________ through phosphorylation, which will bind to to the cyclic AMP response element (CRE) and activate the target gene for gene transcription. This is why too much (2) can alter gene transcription

1. adenylyl cyclase

2. cAMP

3. PKA

4. CREB

________ can activate a GPCR to lead to many downstreams signals like increasing cAMP by activating adenylyl cyclase. Increasing cAMP will then activate PKA. PKA, in this case, instead of going to the nucleus pores, will phosphorylate a phosphorylase kinase, which activates glyocogen phosphorylase. Glycogen phosphorylase will break down ________

Adrenaline, glycogen

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

a) the activity of phosphatases that turn off G proteins by dephosphorylating G protein alpha subunit

b) the activity of phosphatases that turn GTP into GDP

c) the GTPase activity of G protein alpha subunit.

c) the GTPase activity of G protein alpha subunit.

PI 4, 5 -biphosphate gets cleaved by phospholipase C-B (something that gets activated via GPCR) which will produce diacylglycerol and the secondary messenger _______

IP3

When IP3 to Ca2+ receptor, lots of ________ is released

calcium

(1) _______ is released by (2)_______ cells to relax blood vessels in smooth cells via paracrine signaling.

1. Nitric oxide

2. epithelial cells

After IP3 causes the release of calcium, the calcium activates ________ which will convert arginine to to NO. NO will then be released from the epithelial cell and bind to guanylyl cyclase inside a smooth muscle cell in order to relax it.

NO synthase

GPCR can get phosphorylated by a kinase which will allow __________ to bind to it and prevent g protein binding and desensitize the GPCR.

arrestin

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............

a) negative feedback with a long delay

b) persisting positive feedback.

c) 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

remember how when it binded to the regulatory subunits it released the two catalytic subunits

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

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

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

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

A) 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

cGMP is what relaxes the smooth muscle cells

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.

If it cant ever turn off, then you have some issues

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...................

a) binding of arrestin to phosphorylated GPCR.

b) dephosphorylation of GPCR.

c) continued interaction with G protein.

a) binding of arrestin to phosphorylated GPCR.

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

a) a rise in magnesium levels.

b) a drop in cytosolic calcium levels.

c) an inhibition of calcium release from ER.

d) release of calcium from ER into cytosol.

d) release of calcium from ER into cytosol.

RTKs are a branch of enzyme coupled receptors. One of them is already a dimer, whereas all the others are monomers that need to be dimerized. Which one is it?

IGF-1 receptor

How are tyrosine kinase domains activated?

transautophosphorylation- each monomer phosphorlates each other and generates phosphorylated binding sites for signaling proteins.

EGF receptor kinase is activated by trans-autophosphorylation. True or false

False, it is activated by conformational changes. EGF receptor

EGF receptor is made up of ________ and ________ domain

C-terminal tail and kinase domain. The C terminal tail (receiver) does the phosphorylation and the kinase domain (activator) pushes against the receiver to cause a conformational change, which leads to the the receiver phosphorylating itself and the activator.

Signaling proteins with SH2 domains bind to activated receptor kinases. What binding site on SH2 ensures there is specificity?

amino acid binding site. There is also a binding phosphotyrosine binding site but that is so that it can bind to the receptor.

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

transautophosphorylation

Grb2 is an adapter protein that connects the RTK to Ras-GEF. True or false

true, this turns Ras-GEF on so it can make the GDP in Ras to become GTP

Ras can activate MAPKKK, aka Raf, which in return activates _____ through ATP hydrolysis

MAPKKK (raf) --> MAPKK (mek) --> MAPK (erk) --> changes in gene expression & protein activity

Which of the following mechanism is not directly involved in inactivating an 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 lysomes

a) dephosphorylation by serine/ threonine phosphatases

RTK activates PI3 kinase so that PI(3,4,5) is now a docking site for ________ and _______.

PDK1 and Akt

PDK1 activates Akt, which activates ______

mTORC2

Active Akt dissociates to phosphorylate _____

Bad. Now when Bad comes off the apoptosis inhibitor (Bcl2), the inhibitor is activated and apoptosis is inhibited.

Notch is cleaved _____times by gamma secretase and is triggered by a signal from _______

3; delta (a contact dependent protein)

mutations in gamma secretase indicate....

early onset of alzheimers disease

Without a Wnt signal, beta catenin gets degraded and now it can no longer block _________from inhibiting Lef1/TCF ( Wnt Target Genes are off)

groucho

The activation of notch is irreversible. True or False

True

Which of these statements about nuclear receptors are true?

a) They only enter the nucleus after binding to ligand.

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

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

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

Mutations that disrupt the tyrosine 1009 and 1021 residues in PDGF receptor.............................

a) disrupt the recognition and binding by SH3 domains.

b) disrupt the binding of SH2 domains in PI 3-kinase subunit.

c) disrupt the binding of SH2 domains in phospholipase C-gamma.

d) alter the conformation of SH2 domains in phospholipase C-gamma.

c) disrupt the binding of SH2 domains in phospholipase C-gamma.

PI 3-kinase ......

a) activates PDK1 by phosphorylating a serine residue on the protein.

b) is counteracted by PTEN phosphatase.

c) is only known to be activated by receptor tyrosine kinases.

d) removes phosphate groups from Serine or Threonine residues.

b) is counteracted by PTEN phosphatase.

Which of these do not describe Notch?

a) It is a cell-surface receptor.

b) Notch tail is released to activate translation.

c) 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...................

a) inhibit recognition of Notch by Delta.

b) activate transcription of Notch target genes.

c) inhibit transcription of Notch target genes.

d) activate migration of Notch into nucleus.

c) inhibit transcription of Notch target genes.

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

a) activation of Sos -GEF.

b) inhibition of GTP binding to Ras.

c) exchange of GDP for GTP in R

b) inhibition of GTP binding to Ras.

Activation of the EGF receptor includes which of these mechanisms?

a) Phosphorylation by the activator and the receiver.

b) Conformational change in the receiver.

c) Phosphorylation of both the monmers by only the activator.

d) Momomerization of the receptors upon binding to EGF.

b) Conformational change in the receiver.

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

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

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

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

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

a) 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?

a) mTORC2 is sensitive to drug rapamycin.

b) mTORC1 complex activates AKT directly.

c) mTORC1 is sensitive to rapamycin.

d) mTORC2 activity is dependent on Rag,

c) 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.

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

b) a mutation that prevents RTK-A from binding to GF

c) mutation of tyrosines in RTK that inhibit trans-autophosphorylation.

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

a mutation that prevents RTK-A from binding to GF

All GPCRs act by increasing cAMP?

TRUE

FALSE

FALSE

What domain of son of sevenless (Sos) recruits it to the plasma membrane so that it gets in close proximity to Grb2?

PTB

SH3

SH2

PH

PH

Mutations altering the GPCR binding interface in arrestin are likely to..................

a) inhibit GPCR signaling.

b) inhibit phosphorylation by GPCR kinases.

c) prevent desensitization of GPCRs.

d) inhibit G-protein activation.

prevent desensitization of GPCRs.

For Notch to be recognized by Delta, it has to be transported to the..............

golgi lumen

plasma membrane

endoplasmic reticulum

nucleus

plasma membrane

PI3 Kinase primarily phosphorylates...............

tyrosine residues

serine residues

threonine residues

phospholipids

phospholipids

Which of these enzymes is bound to the cytosolic side of the plasma membrane and converts PI(4,5)P2 to IP3 and diacylglycerol?

PKA

Adenylyl cyclase

phospholipase C-Beta

PI 3-kinase

phospholipase C-Beta

Why doesn't the beta subunit of the trimeric G-protein need a lipid anchor like the alpha and gamma subunits?

a) it effectively uses the alpha's anchor.

b) it effectively uses the gamma's anchor.

c) it does not need to be near the plasma membrane.

d) it uses a PH domain to bind a phosphoinositide docking site.

b) it effectively uses the gamma's anchor.

Select the mechanism of activation of AKT by PI-3K ?

a) It phosphorylates lipids that create a docking site for AKT.

b) It activates the receptor tyrosine kinase activity to directly phosphorylate AKT.

c) it is a kinase that directly phosphorylates AKT.

d) It creates DAG and IP3 that activate AKT.

a) It phosphorylates lipids that create a docking site for AKT.

G-proteins are bound to GPCRs......................

a) at the extracellular surface of the plasma membrane.

b) at the intracellular side of the plasma membrane.

c) deep within the alpha-helical pocket in the GPCRs.

d) buried fully within the lipid bilayer.

b) at the intracellular side of the plasma membrane.

Mutations in Ras are found in a majority of cancers. Which of these mutations will lead to permanent activation of Ras-signaling?

a) Mutations that inhibit Ras-GTPase activity

b) Mutations that activate Ras-GAP

c) Mutations that inhibit Ras-GEF activity

d) Mutations that inhibit Raf-activity

a) Mutations that inhibit Ras-GTPase activity

Which of these kinases is activated by binding to diacylglycerol that is released by breakdown of PI(4,5)P2?

Protein Kinase A

Adenylyl cyclase

Protein Kinase C

Phospholipase