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Pharmacology-Au15 > Cell Signaling. Exam 1 > Flashcards

Cell Signaling. Exam 1 Flashcards

1
Q

Ligand activated ion channels can be on the ______ or within an ________.

A

plasma membrane

organelle

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2
Q

How can drugs affect ligand activated ion channels?

A

by influencing synaptic transmission at different loci

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3
Q

Liberation of which ion will have a profound effect on cells?

A

Ca ++

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4
Q

What are four important mechanisms/receptors of cell signaling?

A
  1. Ligand activated ion channels
  2. G-protein coupled receptors
  3. Tyrosine-Kinase receptors
  4. Ligand Activated Nuclear/Transcription receptors
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5
Q

What are the two mechanisms of action for Ligand Activated Nuclear receptors?

A

Class One Nuclear Receptors

Class Two Nuclear Receptors

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6
Q

Earl Sutherland determined that hormonal activation of liver phosphorylase is mediated by ______ and he deemed this a __________.

A

cAMP

Second Messenger

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7
Q

What kind of enzymes were determined by Krebs and Fischer to be important in the phosphorylation cascade?

A

Kinase enzymes

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8
Q

What type of receptor is responsible for signalling in excitable cells and is commonly within the plasma membrane?

A

Ligand-Activated Ion Channels

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9
Q

Ligand-Activated Ion Channels are ______ proteins that produce _______ (with local effect).

A

multisubunit

graded potentials

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10
Q

Signaling in excitable cells is done via Ligand-Activated Ion Channels that either _____ or _____ the cell.

A

Depolarize

Hyperpolarize

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11
Q

Which ion is commonly associated with depolarization of the plasma membrane?

A

Sodium (Na+)

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12
Q

Which ion is commonly associated with hyperpolarization of the plasma membrane?

A

Chloride (Cl-)

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13
Q

Activating and inhibiting ____________ channels is the basis of synaptic transmission of nerve impulses (lots of drugs are targeted here).

A

Ligand Activated Plasma Membrane Ion

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14
Q

What are four ways in which drugs might affect Ligand Activated Ion channels at the plasma membrane?

A 
Affect synaptic transmission:
1. Mimic or Block actions of neurotransmitters
2. Block the channel
Affect at the synaptic cleft:
3. Influence transmitter reuptake
4. Transmitter metabolism
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15
Q

Which organelle is commonly associated with Ligand Activated Ion Channels?

A

Endoplasmic Reticulum (Calcium)

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16
Q

What second messenger is responsible for mediated calcium release from the internal stores of the ER?

A

IP3 (inositol triphosphate)

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17
Q

Which complex is associated with most of the cell signalling that involves calcium?

A

Calcium-Calmodulin

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18
Q

The increase in calcium in the cytoplasm, due to signaling by _____, will thus increase binding of calcium to _______.

A

IP3

calmodulin

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19
Q

What happens after cytoplasmic calcium increases and then binds with calmodulin?

A

The Ca++-Calmodulin Complex is able to interact and ACTIVATE numerous EFFECTOR PROTEINS

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20
Q

How many calcium must bind to calmodulin in order to form the complex?

A

4 calcium

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21
Q

What are two important examples of protein activation by Ca++-Calmodulin? (remember there are about 300 proteins that bind to this complex, this is just two discussed).

A
  1. Calcium-Calmodulin dependent protein kinase

2. Nitric Oxide Synthase

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22
Q

Nitric Oxide Synthase acts in endothelial and neuronal cells to activate ________ from Nitric Oxide precursors.

A

Guanylate Cyclase

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23
Q

G-protein coupled receptors consist of a single polypeptide and seven ________.

A

transmembrane alpha helices

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24
Q

Approximately how many drugs target G-Protein Coupled Receptors?

A

40%

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25
Q

How do agonists activate G-Protein Coupled Receptors?

A

They bind to the receptor and alter the protein’s conformation which leads to the activation of a trimeric G protein

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26
Q

What are the four steps in the G Protein Cycle?

A
  1. Ligand binds and stimulates GDP-GTP exchange
  2. G Protein complex breaks into two pieces: G-alpha and G-BetaG-gamma
  3. G-alpha is involved in GTP hydrolysis (beta-gamma has downstream effects)
  4. The complex reassembles
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27
Q

The GTPase activity is intrinsic to which part of the G-protein?

A

G-alpha

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28
Q

Hydrolyzation of GTP to GDP and Pi is accelerated by which proteins?

A

RGS proteins

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29
Q

Both pieces of the G-Protein complex will participate in ________ but the piece with the major activity is ____.

A 
signalling events (activation of other proteins in the cell)
G-alpha
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30
Q

How many classes of G-alpha proteins are there?

A

Five

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31
Q

How are the five classes of G-alpha proteins distinguished?

A

classes are based on what they activate

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32
Q

What is the major effector of G-alpha?

A

Adenylate Cyclase

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33
Q

How is ATP converted to cAMP?

A

Adenylate Cyclase

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34
Q

cAMP will activate _________ which will phosphorylate a large number of proteins and produce a large number of biological effects.

A

Protein Kinase A

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35
Q

An increase in G-alphas will stimulate _______ to break ______ into cAMP which activates _______ and leads to the phosphorylation of a large number of proteins.

A

Adenylate Cyclase
ATP
PKA

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36
Q

What important enzyme does cAMP activate?

A

Protein Kinase A

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37
Q

What does PKA do?

A

alters the activity of many target proteins via phosphorylation

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38
Q

How can PKA and other protein kinases lead to changes in gene expression in cells?

A

by phosphorylating transcription factors (causing dimerization)

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39
Q

How can PKA affect glucose in the liver?

A

PKA mobilizes glucose in the liver by starting a phosphorylation cascade that activates glycogenolysis

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40
Q

How do G-Protein coupled receptors influence signaling molecules in the plasma membrane?

A

Signaling molecules are embedded within phospholipids in the membrane, the GPCRs activate PHOSPHLIPASEs and liberate the molecules

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41
Q

G-alpha will activate phosphlipases in the membrane wihich will then liberate signaling molecules. What is the importance in activating Phospholipase A2?

A

PLA2 will activate arachidonic acid… which is the source of eicosinoid signaling molecules

42
Q

What are eicosinoid signaling molecules? Where do they come from?

A

Molecules involved in inflammation and immunity: Prostaglandins, leukotrienes, thromboxanes
They come from arachidonic acid

43
Q

What two important signaling molecules are derived from PLC-beta mediated hydrolysis?

A

DAG

IP3

44
Q

What is PIP2?

A

a minor phospholipid component of cell membranes that is a substrate for important signaling molecules.

PIP functions as an intermediate in the IP3/DAG pathway

45
Q

PIP2 is the phospholipid that serves as the substrate for ______.

A

Phospholipase C

46
Q

Cleavage of PIP2 by PLC yields ______ and _____ via hydrolysis.

A

DAG

IP3

47
Q

What is a main difference between DAG and IP3?

A

DAG binds and remains on the cell membrane to activate PKC.

IP3 enters into the cytoplasm and activates receptors on the ER which mobilizes calcium.

48
Q

True or False: DAG mobilizes calcium from the smooth ER.

A

False. Those are actions of IP3

49
Q

DAG activates ________.

A

Protein Kinase C

50
Q

The PKC gene family is _______ dependent.

A

calcium

51
Q

How does DAG regulate PKC binding of calcium?

A

DAG allows the PKC to bind calcium more tightly which allows the enzyme to function at lower calcium concentrations.

52
Q

Which part of the G-protein complex plays a critical role in turning off the GPCRs?

A

G-betaG-gamma

53
Q

G-betaG-gamma helps to ________ the trimeric G protein to the membrane.

A

localize

54
Q

True or False: The trimeric G protein gets turned on, but it turns itself off.

A

True. signalling molecules turn the G protein on, GbetaGgamma turns it off.

55
Q

Because the G protein turns itself off, the agonist is free to activate other G proteins. However, the signal does not last forever. Why?

A

The receptor eventually gets turned off by a process known as desensitization.

56
Q

Describe the steps in G-Protein receptor desensitization.

A
  1. Phosphorylation by a GRK prepares a receptor for arrestin binding
  2. Binding by a beta-arrestin stops further signaling
  3. Formation of a clathrin-coated pit
  4. Endocytosis
57
Q

What is arrestin?

A

a family of proteins important for regulating cell signaling: binding blocks further G protein-mediated signaling, targets receptors for internalization, and redirects signaling to alternate pathways

58
Q

After endocytosis, what are the possible fates of the GPCR?

A
  1. Recycling

2. Degradation

59
Q

The G Protein receptor is desensitized within an ______ by dephosphorylation.

A

endosome

60
Q

If the receptor is sent for recylcing, it is ______ within the endosome.

A

resensitized

61
Q

If the receptor is sent for degradation, it is does this within a ______.

A

lysozome

62
Q

What is the importance of receptor desensitization?

A

Sometimes drugs are administered chronically which can lead to loss of responsiveness to the drug

63
Q

Cell signaling that involves receptor tyrosine kinases (RYKs) will either contain a ______ or ______ tyrosine kinase enzyme.

A

Intrinsic

Extrinsic

64
Q

What occurs to RYKs after a ligand binds?

A

ligand binding leads to dimerization of the receptor

65
Q

Name three examples of possible ligands that would bind to RYK.

A

Growth Factors
Differentiation Factors
Cytokines

66
Q

Receptor dimerization of RYKs will be of what forms?

A

Homodimers
Heterodimers
a combination of both

67
Q

Dimerization (whether homo or hetero) will lead to ________ of the receptors.

A

transphosphorylation

68
Q

What will occur after phosphorylation of tyrosine receptors?

A

signaling molecules will dock on the outer side of the membrane and will pass that signal to a protein on the inside of the membrane

69
Q

After a signaling molecule binds to the RYK in the membrane, how are different signaling cascades initiated?

A

The position of proteins near the inside of the membrane will determine which cascade is begun

70
Q

______-domains on proteins will bind to receptors and allow activation of many signaling pathways

A

SH2

71
Q

True or False: The MapKinase pathway begins with binding to Grb2 through the FH1-demain

A

False: Grb2 is activated through the SH2 domain (a common activator of many signaling proteins)

72
Q

In the Map Kinase Pathway, signaling molecules bind and activate the membrane receptor which will bind to Grb2. Grb2 will then bind with _______ in order to activate _____.

A

SOS

Ras

73
Q

After Ras is activated by Grb2-SOS, the protein kinase activity of _____ will be turned on and it will phosphorylate ______ to start the cascade.

A

Raf

MEK

74
Q

What is the end result of the Map Kinase Pathway?

A

Transcriptional regulation through the phosphorylated transcription factors

75
Q

In the MapK Pathway: Raf, Mek1/2, and ERK1/2 are all _____.

A

Protein kinases

76
Q

Phosphorylation of transcription factors by PKA and other protein kinases can lead to ________ in cells.

A

changes in gene expression

77
Q

Which protein in the Map Kinase pathway is commonly associated with mutations and cancer?

A

Ras

because it requires other protein modifications to work

78
Q

The Akt signaling cascade is a ______ mediated pathway that pushes the cell toward ______.

A

YKR (tyrosine kinase receptor)

growth and proliferation

79
Q

The JAK-STAT pathway uses which type of receptor?

A

Tyrosine Kinase (YKR)

80
Q

Which signaling pathway is commonly used by cytokines?

A

JAK-STAT

81
Q

Binding of cytokine will initiate phosphorylation of the YKR by ______ kinase which will lead to binding of ______ protein.

A

JAK

STAT

82
Q

JAK Kinase binding to STAT protein will enable phosphorylation and ________ of the STAT protein.

A

dimerization

83
Q

After STAT has dimerized, it is translocated to the nucleus where it activates _______.

A

transcriptional panels of genes

84
Q

STAT monomers contain both a _______ and a _______ that can be phosphorylated.

A

SH2-domain

Tyrosine

85
Q

True or False: STAT is slow.

A

False. it is fast.

86
Q

How does an inactive STAT differ from an active STAT?

A

Inactive: monomers of SH2 and tyrosine
Active: dimers, SH2-Y-Phosphate
(“Y” = tyrosine)

87
Q

STAT proteins mediate the profound biological responses to _______.

A

Cytokines

88
Q

Looking at one signaling pathway may not be a good predictor of what is actually happening in the cell because there is _______ among pathways that creates complex signaling.

A

Cross-Talk

89
Q

________ are receptors for steroid hormones.

A

Nuclear Hormone Receptors

90
Q

Nuclear hormone receptors are receptors for _______ such as________.

A

Steroid hormones:

glucocorticoids, mineralocorticoids, testosterone, estrogen, progesterone (also T3/T4, Vit.D, and retinoic acid)

91
Q

Nuclear receptors are characterized as either _____ or _____.

A

Class I

Class II

92
Q

Class I Nuclear receptors exist as a _______ with ______ in the absence of ligand.

A

complex

heat shock proteins

93
Q

Class II Nuclear receptors _______ at a specific response element and binds __________ in the absence of ligand.

A

bind to target DNA
corepressors
(they are not in a huge complex like Class I)

94
Q

Once ligand binds to Class I receptors, what will happen?

A

The complex falls apart, a homodimer forms and then it binds to a specific DNA response element. Binding to DNA stimulates transcription through coactivators.

95
Q

True or False: Class I Nuclear Receptors bind to DNA and utilize corepressors to stimulate transcription.

A

False: COACTIVATORS

96
Q

True or False: Class II Nuclear Receptors utilize coactivators and corepressors, whereas Class I only utilize coactivators.

A

True. Class I are inactive because they are complexed. Class II stay inactive with corepression

97
Q

Glucocorticoids and androgens utilize ______ Nuclear Receptors.

A

Class I

98
Q

Throid hormones, Vitamin D, and retinoic acid utilize _______ Nuclear Receptors.

A

Class II

99
Q

Steriod hormones bind to receptors and then the ligand–receptor complex binds to ________ to increase its expression.

A

specific DNA sequences on target genes

100
Q

What are the fourth methods of cell signaling?

A
  1. Ligand activated ion channels
  2. G protein coupled receptors
  3. Tyrosine Kinase Receptors
  4. Ligand activated Nuclear Receptors

Pharmacology-Au15 (4 decks)

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