Topic 5 - Cell Signalling 2 Flashcards

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1
Q

Describe the speed and time course of contact-dependent signaling

A

Fast - less than a second to minutes

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2
Q

Describe the speed and timescale of signalling where molecules are relayed through the bloodstream

A

Slow - minutes to hours

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3
Q

Slow signalling typically involves altering…

A

Gene transcription

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4
Q

Fast signalling typically involves altering…

A

Specific proteins via phosphorylation, allosteric changes in ion channels, or actin rearrangements for example

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5
Q

Describe the difference between primary and secondary responses to a signal of a cell

A

Primary response: Signal induces transcription of a functional protein which acts to change cell behaviour

Secondary: Signal induces transcription of a transcription factor (protein 1) which then induces the production of a second protein which will exert effects causing a change in cell behaviour

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6
Q

What are 4 key ways in which cells are equipped to react to the same ligand (e.g. ACh) in different ways?

A
  1. Different receptors present
  2. Different intracellular signaling proteins present
  3. Different effector proteins present
  4. Different genes activated
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7
Q

In cells with the same intracellular machinery, how are they able to react to a signal in different ways?

A

Some ligands/factors are area-specific and create GRADIENTS, so the cell reacts to different concentrations of the molecule in different ways

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8
Q

Gradients of morphogens in animals are particularly important during…

A

Development

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9
Q

What are the 2 ways a morphogen can have a concentration gradient?

A
  1. Morphogen is area-specific

2. Morphogen is uniformly distributed but an antagonist for the morphogen is area-specific

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10
Q

Large intracellular signalling molecules can be… (kind of molecule)

A

Proteins exclusively (with very few exceptions)

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11
Q

What is the purpose of a scaffold protein?

A

Arranges proteins in a signal cascade in the correct order for succinct signalling

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12
Q

Integration of 2 signalling pathways requires a molecule which is activated by…

A

Coincidence detection

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13
Q

What is the purpose of anchoring in a signal pathway?

A

Anchors signalling molecules so the signal is localized

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14
Q

(1) and (2) are examples of modulators in a signal transduction pathway

A

Activators and inhibitors

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15
Q

Molecular switches have two conformations, which are…

A

Active and inactive

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16
Q

Monomeric GTPases are activated by…

A

GTP-binding induced by GEF

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17
Q

What are the 2 kinds of common molecular switches? (I.e. modes of “switching”)

A

Phosphorylation

GTP-hydrolysis

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18
Q

How many protein kinases are there in the human genome?

A

520

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19
Q

How many protein phosphatases are there in the human genome?

A

150

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20
Q

What is the difference between a phosphatase and a kinase?

A
Kinase = phosphorylates
Phosphatase = removes phosphate groups
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21
Q

What are the 2 classes of molecules that signal using GTP binding?

A

Large trimeric g-proteins

Monomeric GTPases

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22
Q

What are 2 common kinds of kinases?

A
  1. Serine/threonine kinases

2. Tyrosine kinases

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23
Q

Scaffold proteins serve to minimize (1) and increase (2) of signalling pathways

A
  1. Cross talk

2. Specificity

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24
Q

What is the disadvantage of a pathway using a scaffold protein?

A

Not a lot of opportunity for amplification of the signal

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25
Q

Docking sites on a scaffold proteins are often created by…

A

Phosphorylating the scaffold

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26
Q

Describe how PIPs can be used as docking sites in signalling pathways

A

PIPs can be phosphorylated by receptors when they are activated, this attracts the binding of intracellular signalling proteins

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27
Q

What is a major purpose of a scaffold protein other than localizing things in the correct order?

A

Protein signals have to be in the right order but also in the right ORIENTATION, scaffolds maintain proper orientation so the proteins can interact

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28
Q

If a scaffold is modified to contain a flexible linker, what happens?

A

The scaffold is less effective, it is less able to orient signal molecules in the correct directions

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29
Q

Describe the response of a signalling pathway in which the curve of concentration:response is sigmoidal

A

After a certain threshold concentration of a molecule is reached, the response is amplified

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30
Q

Define desensitization

A

Prolonged exposure to a stimulus decreases a cell’s response to the stimulus

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31
Q

What is the largest family of cell surface receptors?

A

GPCRs

32
Q

What kind of pathways do GPCRs activate?

A

Sensory - sight, smell, taste

33
Q

How many transmembrane regions are there in a GPCR?

A

7

34
Q

What percentage of modern drugs activate or affect GPCRs?

A

50%

35
Q

What domains are present on the alpha subunit of a G-protein?

A

Ras domain (GTPase activity) and AH domain

36
Q

What turns off the enzyme activity of a G-protein?

A

The alpha subunit binding to a regulator of G-protein signalling (RGS)

37
Q

Which of the 3 subunits of a G-protein are lipid-anchored to the membrane?

A

Alpha and gamma

38
Q

Which subunit of the G-protein heterotrimer binds GDP/GTP

A

Alpha

39
Q

Which 2 of the G-protein heterotrimer subunits tend to act together as a single signalling factor?

A

Beta and gamma

40
Q

Rapid response in signalling requires rapid… (2)

A
  1. Synthesis

2. Breakdown

41
Q

How can the activity of cAMP be increased in the cell?

A

By stimulating a Gs heterotrimer

42
Q

Describe the subunits of PKA

A

2 regulatory subunits, 2 catalytic subunits

43
Q

CREB only binds to its response element once…

A

It has been phosphorylated

44
Q

CREB requires both phosphorylation and association of (1) for activation

A

a transcriptional coactivator, CREB-binding protein

45
Q

Pi 4,5-bisphosphate is cleaved into… (2)

A

Diacylglycerol and IP3

46
Q

What cleaves PI 4,5-bisphosphate into its 2 components?

A

A Gq subunit

47
Q

Diacylglycerol goes on to activate…

A

Protein kinase C

48
Q

IP3 goes on to…

A

Enduce the release of Ca++ from the sarcoplasmic reticulum

49
Q

To inhibit increase in Ca++ in the cytoplasm, it is useful to…

A

Phosphorylate IP3 into IP4 or IP2

IP3 is the only inositide that can bind to calcium channels

50
Q

The most important calcium binding protein is…

A

Calmodulin

51
Q

What makes calmodulin highly adaptable so that it can bind many types of proteins of different shapes?

A

Has a “cable” region which allows it to bend and wrap around other proteins

52
Q

What are the 2 kinds of domains that make up a CamKII complex?

A

Hub domains and kinase domains

53
Q

What are the states of CamKII? (4)

A

Active
Inactive
Partially active
Ca-independent, 50-80% active

54
Q

With one kinase domain active, CamKII is in the…

A

Partially active state

55
Q

With 2 kinase domains activated, CamKII is in the (1) state

A

Active

56
Q

With no kinase domains active, but CamKII is still phosphorylating, what state is the complex in?

A

The Ca++-independent state

57
Q

CamKII is involved in the important process of (1) in vertebrates

A

Learning and memory

58
Q

Describe the effects of ACh on heart muscle cell contractions (pathway)

A

ACh binds and activates Gi protein > alpha subunit inhibits AC > beta-gamma subunit opens K+ channels

59
Q

Why is it important to open K+ channels to reduce strength of contractions of heart muscles?

A

Because if K+ is high in the cell it is more difficult to depolarize it

60
Q

What are the three ways in which GPCRs can become desensitized?

A
  1. Receptors inactivated
  2. Receptors sequestered
  3. Receptors downregulated
61
Q

What is a GRK?

A

GPCR kinase

62
Q

What are 2 examples of GRKs?

A

PKA and PKC

63
Q

What molecule binds to a GPCR which will eventually lead to signal desensitization?

A

Arrestin

64
Q

Do GPCRs and enzyme-coupled cell surface receptors always activate the same signalling pathways?

A

No - sometimes lead to the same pathway, a lot of cross-linkage

65
Q

How many transmembrane domains are there on an enzyme-coupled cell surface receptor?

A

1

66
Q

An example of na enzyme-coupled cell surface receptor with intrinsic kinase activity is this class of receptors

A

RTKs

67
Q

How can a conformational change occur in a receptor (like an RTK) with only one transmembrane domain?

A

The receptors can dimerize

68
Q

Phosphorylation of enzyme-coupled cell surface receptors forms a transient sort of…

A

Scaffold

69
Q

What is special about the activation of epidermal growth factor receptors?

A

Both subunits of the dimer are phosphorylated but only one is activated

70
Q

Do epidermal growth factor receptors undergo transautophosphorylation?

A

No - only one of the dimers does the phosphorylating

71
Q

Adaptor proteins in RTK activation are composed largely of these 2 kinds of domains

A

SH2 and SH3

72
Q

What molecule does Ras activate?

A

MAPK

73
Q

The order of the boring naming scheme of the Ras-MAPK pathway is (in order…)

A

Raf, Mek, Erk

74
Q

How is cross-talk between parallel MAPK modules avoided?

A

Scaffolds

75
Q

RTK can activate phosphoinositide 3-kinase to create…

A

Docking sites for signalling molecules