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Biology 360 > Topic 5 - Cell Signalling 2 > Flashcards

Topic 5 - Cell Signalling 2 Flashcards

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
Docking sites on a scaffold proteins are often created by...
Phosphorylating the scaffold
26
Describe how PIPs can be used as docking sites in signalling pathways
PIPs can be phosphorylated by receptors when they are activated, this attracts the binding of intracellular signalling proteins
27
What is a major purpose of a scaffold protein other than localizing things in the correct order?
Protein signals have to be in the right order but also in the right ORIENTATION, scaffolds maintain proper orientation so the proteins can interact
28
If a scaffold is modified to contain a flexible linker, what happens?
The scaffold is less effective, it is less able to orient signal molecules in the correct directions
29
Describe the response of a signalling pathway in which the curve of concentration:response is sigmoidal
After a certain threshold concentration of a molecule is reached, the response is amplified
30
Define desensitization
Prolonged exposure to a stimulus decreases a cell's response to the stimulus
31
What is the largest family of cell surface receptors?
GPCRs
32
What kind of pathways do GPCRs activate?
Sensory - sight, smell, taste
33
How many transmembrane regions are there in a GPCR?
7
34
What percentage of modern drugs activate or affect GPCRs?
50%
35
What domains are present on the alpha subunit of a G-protein?
Ras domain (GTPase activity) and AH domain
36
What turns off the enzyme activity of a G-protein?
The alpha subunit binding to a regulator of G-protein signalling (RGS)
37
Which of the 3 subunits of a G-protein are lipid-anchored to the membrane?
Alpha and gamma
38
Which subunit of the G-protein heterotrimer binds GDP/GTP
Alpha
39
Which 2 of the G-protein heterotrimer subunits tend to act together as a single signalling factor?
Beta and gamma
40
Rapid response in signalling requires rapid... (2)
1. Synthesis | 2. Breakdown
41
How can the activity of cAMP be increased in the cell?
By stimulating a Gs heterotrimer
42
Describe the subunits of PKA
2 regulatory subunits, 2 catalytic subunits
43
CREB only binds to its response element once...
It has been phosphorylated
44
CREB requires both phosphorylation and association of (1) for activation
a transcriptional coactivator, CREB-binding protein
45
Pi 4,5-bisphosphate is cleaved into... (2)
Diacylglycerol and IP3
46
What cleaves PI 4,5-bisphosphate into its 2 components?
A Gq subunit
47
Diacylglycerol goes on to activate...
Protein kinase C
48
IP3 goes on to...
Enduce the release of Ca++ from the sarcoplasmic reticulum
49
To inhibit increase in Ca++ in the cytoplasm, it is useful to...
Phosphorylate IP3 into IP4 or IP2 IP3 is the only inositide that can bind to calcium channels
50
The most important calcium binding protein is...
Calmodulin
51
What makes calmodulin highly adaptable so that it can bind many types of proteins of different shapes?
Has a "cable" region which allows it to bend and wrap around other proteins
52
What are the 2 kinds of domains that make up a CamKII complex?
Hub domains and kinase domains
53
What are the states of CamKII? (4)
Active Inactive Partially active Ca-independent, 50-80% active
54
With one kinase domain active, CamKII is in the...
Partially active state
55
With 2 kinase domains activated, CamKII is in the (1) state
Active
56
With no kinase domains active, but CamKII is still phosphorylating, what state is the complex in?
The Ca++-independent state
57
CamKII is involved in the important process of (1) in vertebrates
Learning and memory
58
Describe the effects of ACh on heart muscle cell contractions (pathway)
ACh binds and activates Gi protein > alpha subunit inhibits AC > beta-gamma subunit opens K+ channels
59
Why is it important to open K+ channels to reduce strength of contractions of heart muscles?
Because if K+ is high in the cell it is more difficult to depolarize it
60
What are the three ways in which GPCRs can become desensitized?
1. Receptors inactivated 2. Receptors sequestered 3. Receptors downregulated
61
What is a GRK?
GPCR kinase
62
What are 2 examples of GRKs?
PKA and PKC
63
What molecule binds to a GPCR which will eventually lead to signal desensitization?
Arrestin
64
Do GPCRs and enzyme-coupled cell surface receptors always activate the same signalling pathways?
No - sometimes lead to the same pathway, a lot of cross-linkage
65
How many transmembrane domains are there on an enzyme-coupled cell surface receptor?
1
66
An example of na enzyme-coupled cell surface receptor with intrinsic kinase activity is this class of receptors
RTKs
67
How can a conformational change occur in a receptor (like an RTK) with only one transmembrane domain?
The receptors can dimerize
68
Phosphorylation of enzyme-coupled cell surface receptors forms a transient sort of...
Scaffold
69
What is special about the activation of epidermal growth factor receptors?
Both subunits of the dimer are phosphorylated but only one is activated
70
Do epidermal growth factor receptors undergo transautophosphorylation?
No - only one of the dimers does the phosphorylating
71
Adaptor proteins in RTK activation are composed largely of these 2 kinds of domains
SH2 and SH3
72
What molecule does Ras activate?
MAPK
73
The order of the boring naming scheme of the Ras-MAPK pathway is (in order...)
Raf, Mek, Erk
74
How is cross-talk between parallel MAPK modules avoided?
Scaffolds
75
RTK can activate phosphoinositide 3-kinase to create...
Docking sites for signalling molecules

Biology 360 (12 decks)

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