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SL12002 Cell Biology > Cell signalling 2 > Flashcards

Cell signalling 2 Flashcards

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1
Q

What kind of receptors are receptor tyrosine kinases

A

An enzyme coupled receptor

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2
Q

What is an enzyme coupled receptor?

A

A receptor that has a cytosolic domain with intrinsic enzyme activity and an extracellular domain where binding occurs

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3
Q

What enzyme activity does receptor tyrosine kinases have?

A

Tyrosine kinase activity

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4
Q

What are RTKs used to mediate?

A

Cell survival, growth and differentiation

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5
Q

How do RTKs mediate cell survival, growth and differentiation?

A

Through growth factor signalling

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6
Q

How do RTKs usually exist?

A

As inactive monomers

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7
Q

What does the binding of a ligand do to two RTK monomers?

A

Brings them together, causing dimerisation

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8
Q

What does dimerisation of the RTKs do to the tyrosine kinase domains?

A

Brings them close together

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9
Q

What do the TKDs do once brought together?

A

Cross autophosphorylate each others tyrosine residues

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10
Q

What do TKDs do once phosphorylated?/

A

Phosphorylate other tyrosine residues outside of the kinase domains

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11
Q

What do the phosphotyrosines do?

A

Serve as docking sites for adaptor/signalling proteins

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12
Q

What do adaptor/signalling proteins do?

A

Propagates the signal to the rest of the cell

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13
Q

What is HER2?

A

An example of an RTK

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14
Q

What does HER2 stand for?

A

Human epidermal growth factor 2

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15
Q

What kind of dimers does HER2 usually form?

A

heterodimers (i.e. HER2 and another epidermal growth factor receptor)

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16
Q

What are some human epidermal growth factors?

A

HER2, HER3, EGFR, HER4

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17
Q

What causes dimerisation between HER3 and HER2?

A

A ligand binding to HER3

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18
Q

What ligand binds to HER3?

A

Neuroglin

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19
Q

What happens after the activation of the HER2 HER3 heterodimer?

A

Grb2 (adaptor protein) docks onto one of the phosphorylated tyrosine kinases from HER2

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20
Q

What can Grb2 also interact with (other than RTK)?

A

Ras-GEF (aka Sos)( a regulatory protein)

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21
Q

What does SOS promote?

A

Inactive Ras (in its GDP bound state) to release GDP in exchange for GTP

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22
Q

What happens to Ras after it exchanges its GDP for a GTP?

A

Ras is activated

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23
Q

Where is Ras found?

A

Membrane bound

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24
Q

What can Ras do once acticated?

A

Can be involved in downstream MAPKinase signalling

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25
What can happen during HER2 overexpression?
HER2 can form homodimers with itself
26
What happens when a HER2 homodimer forms?
The Ras activation can occur regardless of ligand binding
27
What is Ras?
A monomeric G protein with intrinsic GTPase activity
28
Why does Ras have intrinsic GTPase activity?
So it can hydrolyse GTP to GDP if needed
29
Activity of Ras in its GDP bound state?
Inactive
30
Activity of Ras in its GTP bound state?
Active
31
Ras-GEF stands for?
Ras-Guanine Exchange Factor
32
What does Ras GEF do?
Promoted ras to release GDP and take up a GTP
33
How is Ras activated?
By exchanging its GDP for a GTP
34
How is Ras inactivated?
By using its intrinsic GTPase activity to hydrolyse its GTP
35
What is the role of Ras-GAP?
It promotes the hydrolysis of the GTP in Ras GTP
36
Easier name for MAP kinase kinase kinase??
Raf
37
What does MAP stand for?
Mitogen-activated protein
38
What does Ras (GTP) do to Raf?
Activates it
39
What does activated Raf do?
It phosphorylates, and activates Mek
40
What does Raf use to phosphorylate and activate Mek?
ATP
41
What does activated Mek do?
It phosphorylates and activated Erk
42
What does Mek use to phosphorylate and activate Erk?
ATP
43
What can activated Erk do?
Phosphorylate, and thus activate different proteins and transcription factors
44
What can the proteins and transcription factors activated by Erk do?
Promote cell proliferation
45
How is amplification occuring at each stage of the MAP kinase cascade
Each kinase can activate multiple kinases etc etc
46
How could an issue with a kinase pathway lead to cancer?
If the pathway was permanently activated, all steps including the activation of proteins and transcription factors involved in cell proliferation would go on unmitigated--> uncontrollable cell division
47
What is an oncogene?
A muated gene that has the potential to cause cancer
48
What is a proto-oncogene?
Unmutated genes which affect cell proliferation (and could turn into oncogenes if mutated)
49
Why could the Ras genes and the MAPK genes be considered proto-oncogenes?
They are both eventually involved in cell proliferation, and could mutate
50
How is phosphorylation status a signalling switch?
The phosphorylated form of some proteins is the active form, while the dephosphorylated form is the inactive form
51
What catalyses the turning off of a phosphorylated, activated protein?
Protein phosphotase
52
Where does PI3kinase bind to in the PI3K pathway?
The phosphotyrosine onto HER3
53
What happens to PI3K after it docks onto the phosphotyrosine on HER3?
It is activated
54
What type of kinase is PI3K?
A lipid kinase
55
What does PI3K uses PIP2 for?
As a substrate to generate PIP3
56
Where are PIP2 and PIP3 found?
Membrane bound
57
What do some protein regions of proteins such as protein kinase 1 and Akt allow?
High affinity binding to PIPs
58
What are the domains that allow certain proteins to bind to PIPs?
Pleckstrin Homology Domains
59
What do Protein kinase 1 and Akt use PIP3 as?
A docking site, allowing them to be brought to the plasma membrane
60
What does protein kinase 1 do to Akt once they are both at the plasma membrane?
It phosphorylates, and activates it
61
What does Akt do immediately after being phosphorylated?
It dissociates from the PIP and the plasma membrane
62
What process is Akt important in?
Cell survival
63
What is active Akt?
A serine/threonine kinase
64
What does active Akt do to Bad?
Akt phosphorylates Bad
65
What does Bad do in its active form?
It holds Bcl2 in its inactive state
66
What does the phosphorylation of Bad do?
Changes Bad's conformation, causing it to release Bcl2
67
What does the release of Bcl2 from bad to to Bcl2?
Activates it
68
What is the role of active Bcl2
Promotion of cell survival by inhibition of apoptosis
69
How does active Akt mediate cell growth?
Through other signalling events, it ends up activating mTor
70
What does mTor do once activated?
Inhibits protein degradation and stimulates protein synthesis
71
Where does phospholipase C gamma bind to?
A phosphotyrosine of HER3
72
What does phospholipase C gamma use PIP2 for?
As a substrate to generate DAG (diacyl glycerol) and IP3 (inositol triphosphate)
73
Where is IP3 sent after it is generated?
To the cytosol
74
What does IP3 do once it is in the cytosol?
It binds to, and opens calcium channels in the ER
75
What is the direct effect of IP3 binding to Ca2+ channels on the ER?
The cytosolic concentration of Ca2+ increases
76
What does DAG do once generated?
Recruits and activates protein kinase C (PKC)
77
What can cytosolic ca2+ bind to?
PKC
78

SL12002 Cell Biology (14 decks)

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