Chapter 16 - Part II - Cell Signaling

Question 1

Many actions trigger an increase in intracellular Ca2+ concentrations. a) sperm fertilization an egg cell = ? b) nerves signaling muscle cells = ? c) secretory cells (including neurons) = ?

Answer 1

a) development b) contraction c) secretion

Question 2

Ca2+ can trigger biological effects 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.

Answer 2

low (10^-7M); extracellular 10^-3M; ER

Question 3

Ca2+ binds and affects the action of ____ proteins like _____.

Answer 3

Ca2+ responsive ; calmodulin

Question 4

Calmodulin activates ______.

Answer 4

CaM-kinases (Ca2+/Calmodulin dependent protein kinases)

Question 5

Calmodulin has a dumbbell shape, with 2 globular ends connected by a long alpha helix. Each end has ____ Ca2+-binding domains. Conformational changes in Ca2+/calmodulin that occur when it binds to an isolated segment of a target protein. In this conformation, the ___ helix jackknifes to surround the target.

Answer 5

2; alpha

Question 6

PKA, PKC, CaM-kinases phosphorylate selected signaling and effector proteins on ___ and ___, thereby altering their activity.

Answer 6

serines; threonines

Question 7

Different cell types contain different sets of signaling and effector proteins and are therefore affected in different ways. True or false?

Answer 7

True

Question 8

GPRC signaling allows for signal ____.

Answer 8

amplification

Question 9

An example of GPRC signaling that allows for signal amplification is __.

Answer 9

Rod photoreceptor cells

Question 10

In the rod photoreceptor cells example, the a) signal = ? b) GPRC = ? c) G-protein = ?

Answer 10

a) light; b) rhodopsin; c) transducin

Question 11

_____ results in the closure of cation channels and a voltage change. Signal is then relayed to the ____.

Answer 11

Signaling cascade; brain

Question 12

Enzyme-coupled receptors often regulate ___, ____, ____ and/or ___.

Answer 12

cell growth; proliferation; differentiation; survival

Question 13

In enzyme-coupled receptors, responses are typically ___, and their effects may require many intracellular transduction steps that usually lead to a change in _____.

Answer 13

slow; gene expression

Question 14

Enzyme-coupled receptors require less steps than GPCR. True or false?

Answer 14

False. It requires more steps.

Question 15

What does RTKs stand for?

Answer 15

Receptor tyrosine kinases

Question 16

RTKs are 7 transmembrane.

Answer 16

False. RTKs are single transmembrane.

Question 17

RTKs are single transmembrane.

Answer 17

true

Question 18

Signal binding to RTKs occur in ___ space.

Answer 18

extracellular

Question 19

Two RTKs __ after signal binding.

Answer 19

dimerize

Question 20

Dimerized RTKs ___ each other.

Answer 20

phosphorylate

Question 21

Intracellular signaling proteins are ___ upon binding to the phosphorylated RTKs.

Answer 21

activated

Question 22

Signaling is turned off when _____ dephosphorylates the RTKs.

Answer 22

protein tyrosine phosphates

Question 23

RTKs are ____ protein that attach _____. And they are also ____.

Answer 23

membrane; phosphates; enzymes

Question 24

Activated RTKs recruit a ___ of intracellular signaling ___.

Answer 24

complex; proteins

Question 25

Mutations in receptor _____ are frequently associated with the human cancer.

Answer 25

Tyrosine kinase

Question 26

Abnormalities in signaling via RTKs have a major role in the development of most ____.

Answer 26

cancers

Question 27

The enzyme that removes phosphates is ________.

Answer 27

phosphatase.

Question 28

These phosphorylated tyrosines attract different intracellular signaling proteins (as many as __ or __ different), which then become activated and pass on the signal.

Answer 28

10; 20

Question 29

Typically, the binding of a signal molecule to the extracellular domain of a receptor tyrosine kinases (RTK) causes two receptor molecules to associate into a ____. The signal molecule is itself a ___ and thus can physically cross-link two receptor molecules; other signal molecules induce a conformational change in the RTKs, causing the receptors to dimerize, too.

Answer 29

dimer; dimer;

Question 30

In either case, ____ brings the kinase domains of each systolic receptor tail into contact with the other; this activates the kinases to ___ the adjacent tail on several ____. Each phosorylated tyrosine serves as a specific docking site for a different intracellular signaling protein, which then helps relay the signal to the cell’s interior.

Answer 30

dimer formation; phosphorylate; tyrosine

Question 31

What 3 intracellular signaling molecules are activated by RTKs?

Answer 31

1- phospholipase C 2- Ras 3- phosphoinositide 3-kinase

Question 32

What generates DAG and IP3?

Answer 32

phospholipase C

Question 33

What monomeric GTPase is attached to the plasma membrane?

Answer 33

Ras

Question 34

What phosphorylates inositol phospholipids?

Answer 34

phosphoinositide 3-kinase (PI 3-kianse)

Question 35

__ is activated when a signal binds a RTK leading to the activation of ___.

Answer 35

Ras; Ras-GEF

Question 36

Most RTKs activate the Monomeric GTPase called ___, and then signaling molecule binding.

Answer 36

Ras

Question 37

___ helps activate the GTP binding protein by promoting its binding to GTP.

Answer 37

GEF

Question 38

An adaptor protein docks on a particular phosphotyrosine on the activated receptor. The adaptor recruits a Ras guanine nucleotide exchange factor ____ that stimulates Ras to exchange its bound GDP for GTP.

Answer 38

Ras-GEF

Question 39

These monomeric GTP-binding proteins are aided by two sets of regulatory proteins. ___ activate the switch proteins by promoting the exchange of GDP for GTP. And ___ turn them off by promoting GTP hydrolysis.

Answer 39

GEFs; GAPs

Question 40

If Ras contains a mutation that leads to a defect in GTP hydrolysis, this could fuel uncontrolled proliferation in cancer because…

Answer 40

Ras is able to signal to downstream pathways inappropriately

Question 41

Activated Ras initiates the ___ signaling module.

Answer 41

MAP

Question 42

Activated Ras protein initiates the ___ which activates a 3-kinase signaling module, which relays the signal. The final kinase in the module, ____, phosphorylates various downstream signaling or effector proteins.

Answer 42

MAP kinase signaling module; MAP kinase

Question 43

RTKs are usually activated by - signa;-induced _____; - which allows the receptors to ____ themselves and ___ intracellular signaling proteins that are stimulated by the phosphorylated receptor.

Answer 43

dimerization; phosphorylate; activate

Question 44

After it is activated, the receptor is dephosphorylated, and thereby inactivated, by a _____.

Answer 44

protein tyrosine phosphatase

Question 45

A mutation in the gene that encodes the protein tyrosine phosphatase will in appropriately increase the activity of the receptor and promote _________.

Answer 45

uncontrolled cell profileration

Question 46

A mutation that inactivates the protein tyrosine phosphatase that normally removes the phosphates from tyrosines on the activated receptor promote _____.

Answer 46

uncontrolled cell proliferation

Question 47

Many tumor cell lines have mutations in the gene that encodes receptor tyrosine (RTK). Which of the following types of mutations would be expected to promote uncontrolled cell proliferation?

Answer 47

a mutation that inactivates the protein tyrosine phosphatase that normally removes the phosphates from tyrosine on the activated receptor.

Question 48

RTKs are usually activated by signal-induced ________; which allows the receptors to ____ themselves and activate intracellular signaling proteins that are stimulated by the phosphorylated receptor.

Answer 48

dimerization; phosphorylate

Question 49

____ is often mutated in cancerous cells.

Answer 49

Ras

Question 50

About 30% of human cancers contain mutations in the __ gene.

Answer 50

Ras

Question 51

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?

Answer 51

addition of a drug that blocks protein Y from interacting with its target

Question 52

The Ras protein is always on. True or False?

Answer 52

True

Question 53

Ras protein activates Y protein. And the Y protein sends the signal. True or false?

Answer 53

True

Question 54

If you block the active signaling protein X, does that turn off the signaling in this cell line?

Answer 54

No.

Question 55

If you add a drug that prevents protein X from activating Ras, would that turn off signaling in this cell line?

Answer 55

No. Active Ras protein is ALWAYS on. There will be no effect.

Question 56

Will the addition of a drug that increases the affinity of protein Y and Ras turn off signaling in this cell line?

Answer 56

No. You’re trying to turn off signaling. Increasing the affinity of Y will only increase signaling.

Question 57

____ generates phosporylated inositol phospholipid upon RTK activation.

Answer 57

PI 3-kinase

Question 58

PI 3-kinase generates ____ upon RTK activation.

Answer 58

phosphorylated inositol phospholipid

Question 59

What are docks for proteins (like protein kinase 1 and Akt) that bind and become activated? (Think… what is kinase? when you think of 1, what do you think of? where are they going to bind?)

Answer 59

phosphorylated inositol phospholipid

Question 60

RTKs activate the PI-3-kinase-Akt signaling pathway. An extracellular survival signal, such as IGF, activates an RTK, which recruits and activates _____. This enzyme then phosphorylates an ___ that is embedded in the cytosolic side of the plasma membrane. The resulting phosphorylated inositol phospholipid then attracts intracellular signaling proteins that have a special domain that recognizes it.

Answer 60

PI-3 kinase; inositol phospholipid

Question 61

One of these signaling proteins, ____, is a protein kinase that is activated at the membrane by phosphorylation mediated by two other protein kinases (here called protein kinases 1 and 2); protein kinase 1 is also recruited by the phosphorylated lipid docking sites. Once activated, ____ is released from the plasma membrane and phosphorylates various downstream proteins on specific serines and threonines.

Answer 61

AKT; AKT;

Question 62

Phosphorylation by ___ inactivates proteins that promote cell death.

Answer 62

Akt

Question 63

In phosphorylation by Akt, ___ is the cell-death protein.

Answer 63

Bcl2

Question 64

Overall, Akt ___ cell survival.

Answer 64

promotes

Question 65

Phosphorylation of Bad ____ active Bcl2.

Answer 65

releases

Question 66

Activated Akt promotes cell survival. One way it does so is by phosphorylating and inactivating a protein called ___. In its unphosphorylated state, ____ promotes apoptosis (a form of cell death) by binding to and inhibiting a protein called Bcl2 which otherwise suppresses apoptosis.

Answer 66

Bad; Bad

Question 67

When Bad is phosphorylated by Akt, Bad releases _____, which now blocks apoptosis, thereby promoting _____.

Answer 67

Bcl2; cell survival

Question 68

Which of the following statements is false?

Answer 68

d

Question 69

Phosphorylation by indirectly activates ___, a kinase, which _____ cell growth.

Answer 69

Tor; promotes

Question 70

___, a cancer drug, inactivates Tor.

Answer 70

Rapamycin

Question 71

Akt stimulates cells to grow in size by activating the serine/threonine kinase Tor. The binding of a growth factor to an RTK activates the ____ signaling pathway. Akt then indirectly activates Tor by phosphorylating and inhibiting a protein that helps to keep Tor shut down. Tor stimulates protein synthesis and inhibits protein degradation by phosphorylating key proteins in these processes. The anticancer drug ___ slows cell growth by inhibiting Tor. In fact, the Tor protein derives its name from the fact that is is a target of ____.

Answer 71

Akt; rapamycin; rapamycin

Question 72

In plants, there are RTKs, steroid hormone nuclear receptors, cAMP, and few GPCRs.

Answer 72

False. There are No RTKs, steroid hormone nuclear receptors, cAMP, and few GPCRs.

Question 73

Plants have lots of serine-threonine kinases. True or False?

Answer 73

True

Question 74

In plants, signal binding to an ____ relives transcriptional repression in plants.

Answer 74

ethylene receptor

Question 75

The ethylene response in plants involves:

+ a ___ transmembrane receptor;

+ when the receptor is not bound to ____;

+ the receptor activates a _____.

Answer 75

dimeric; ethylene; protein kinase

Question 76

The ethylene response in plants involves:

+ when the receptor is not bound to ethylene;

+ the receptor activates a protein kinase,

+ which activates an intracellular pathway;

+ that leads to a degradation of a ________ important for transcribing the ethylene-responsive genes;

+ So transcriptional ____ occurs in plants.

Answer 76

transcriptional regulator;

repression

Question 77

Signaling pathways are highly interconnected. True or false?

Answer 77

True

Question 78

So activation of the GPCR depends on what protein?

Answer 78

G protein or

monomeric GTPase (eg. Ras protein.)

Question 79

Intracellular signaling proteins can ___ incoming signals.

Answer 79

integrate

Question 80

A protein kinase can act as an integrating device in signaling if it ______.

Answer 80

is activated by 2+ proteins in different signaling pathways.

Question 81

Calcium ion release triggers all of the following biological processes EXCEPT

Answer 81

action potential transmission along an axon.

Question 82

Shown is a schematic of the light-induced signaling cascade in rod photoreceptor cells. At which step(s) does the response become amplified so that one photon stimulates a multifaceted response?

Answer 82

cyclic GMP phosphodiesterase hydrolyzing cGMP molecules

Question 83

Protein kinase is an enzyme that functions in which of the following ways?

Answer 83

activates or inactivates other proteins by adding a phosphate group to them

Question 84

What role do phosphatases play in signal transduction pathways?

Answer 84

They inactivate protein kinases to turn off signal transduction.

Question 85

Consider this pathway:

epinephrine → G protein-coupled receptor → G protein → adenylyl cyclase → cAMP

The second messenger in this pathway is ________.

Answer 85

cAMP

Question 86

A mutation that knocks out the GTPase activity of a G protein would have what effect on a cell?

Answer 86

The G protein would always be active.

Question 87

The activation of receptor tyrosine kinases is characterized by

Answer 87

dimerization and phosphorylation.

Question 88

Many tumor cell lines have mutations in the gene that encodes receptor tyrosine kinase (RTK). Which of the following types of mutation would be expected to promote uncontrolled cell proliferation?

Answer 88

a mutation that inactivates the protein tyrosine phosphatase that normally removes the phosphates from tyrosines on the activated receptor

Question 89

Shown below is a diagram of how theoretical intracellular signaling pathways could integrate incoming signals to produce a coordinated cell response. Which signal(s) would lead to activation of both kinase 1 and kinase 2?

Answer 89

signals A and D

Question 90

Enzymes that degrade cAMP.

Answer 90

cyclic AMP phosphodiesterase

Question 91

Communication system where the signaling molecule is affecting the secreting cell itself ___________________

Answer 91

autocrine