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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
Q

What can happen during HER2 overexpression?

A

HER2 can form homodimers with itself

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26
Q

What happens when a HER2 homodimer forms?

A

The Ras activation can occur regardless of ligand binding

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27
Q

What is Ras?

A

A monomeric G protein with intrinsic GTPase activity

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28
Q

Why does Ras have intrinsic GTPase activity?

A

So it can hydrolyse GTP to GDP if needed

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29
Q

Activity of Ras in its GDP bound state?

A

Inactive

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30
Q

Activity of Ras in its GTP bound state?

A

Active

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31
Q

Ras-GEF stands for?

A

Ras-Guanine Exchange Factor

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32
Q

What does Ras GEF do?

A

Promoted ras to release GDP and take up a GTP

33
Q

How is Ras activated?

A

By exchanging its GDP for a GTP

34
Q

How is Ras inactivated?

A

By using its intrinsic GTPase activity to hydrolyse its GTP

35
Q

What is the role of Ras-GAP?

A

It promotes the hydrolysis of the GTP in Ras GTP

36
Q

Easier name for MAP kinase kinase kinase??

37
Q

What does MAP stand for?

A

Mitogen-activated protein

38
Q

What does Ras (GTP) do to Raf?

A

Activates it

39
Q

What does activated Raf do?

A

It phosphorylates, and activates Mek

40
Q

What does Raf use to phosphorylate and activate Mek?

41
Q

What does activated Mek do?

A

It phosphorylates and activated Erk

42
Q

What does Mek use to phosphorylate and activate Erk?

43
Q

What can activated Erk do?

A

Phosphorylate, and thus activate different proteins and transcription factors

44
Q

What can the proteins and transcription factors activated by Erk do?

A

Promote cell proliferation

45
Q

How is amplification occuring at each stage of the MAP kinase cascade

A

Each kinase can activate multiple kinases etc etc

46
Q

How could an issue with a kinase pathway lead to cancer?

A

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
Q

What is an oncogene?

A

A muated gene that has the potential to cause cancer

48
Q

What is a proto-oncogene?

A

Unmutated genes which affect cell proliferation (and could turn into oncogenes if mutated)

49
Q

Why could the Ras genes and the MAPK genes be considered proto-oncogenes?

A

They are both eventually involved in cell proliferation, and could mutate

50
Q

How is phosphorylation status a signalling switch?

A

The phosphorylated form of some proteins is the active form, while the dephosphorylated form is the inactive form

51
Q

What catalyses the turning off of a phosphorylated, activated protein?

A

Protein phosphotase

52
Q

Where does PI3kinase bind to in the PI3K pathway?

A

The phosphotyrosine onto HER3

53
Q

What happens to PI3K after it docks onto the phosphotyrosine on HER3?

A

It is activated

54
Q

What type of kinase is PI3K?

A

A lipid kinase

55
Q

What does PI3K uses PIP2 for?

A

As a substrate to generate PIP3

56
Q

Where are PIP2 and PIP3 found?

A

Membrane bound

57
Q

What do some protein regions of proteins such as protein kinase 1 and Akt allow?

A

High affinity binding to PIPs

58
Q

What are the domains that allow certain proteins to bind to PIPs?

A

Pleckstrin Homology Domains

59
Q

What do Protein kinase 1 and Akt use PIP3 as?

A

A docking site, allowing them to be brought to the plasma membrane

60
Q

What does protein kinase 1 do to Akt once they are both at the plasma membrane?

A

It phosphorylates, and activates it

61
Q

What does Akt do immediately after being phosphorylated?

A

It dissociates from the PIP and the plasma membrane

62
Q

What process is Akt important in?

A

Cell survival

63
Q

What is active Akt?

A

A serine/threonine kinase

64
Q

What does active Akt do to Bad?

A

Akt phosphorylates Bad

65
Q

What does Bad do in its active form?

A

It holds Bcl2 in its inactive state

66
Q

What does the phosphorylation of Bad do?

A

Changes Bad’s conformation, causing it to release Bcl2

67
Q

What does the release of Bcl2 from bad to to Bcl2?

A

Activates it

68
Q

What is the role of active Bcl2

A

Promotion of cell survival by inhibition of apoptosis

69
Q

How does active Akt mediate cell growth?

A

Through other signalling events, it ends up activating mTor

70
Q

What does mTor do once activated?

A

Inhibits protein degradation and stimulates protein synthesis

71
Q

Where does phospholipase C gamma bind to?

A

A phosphotyrosine of HER3

72
Q

What does phospholipase C gamma use PIP2 for?

A

As a substrate to generate DAG (diacyl glycerol) and IP3 (inositol triphosphate)

73
Q

Where is IP3 sent after it is generated?

A

To the cytosol

74
Q

What does IP3 do once it is in the cytosol?

A

It binds to, and opens calcium channels in the ER

75
Q

What is the direct effect of IP3 binding to Ca2+ channels on the ER?

A

The cytosolic concentration of Ca2+ increases

76
Q

What does DAG do once generated?

A

Recruits and activates protein kinase C (PKC)

77
Q

What can cytosolic ca2+ bind to?

SL12002 Cell Biology (14 decks)

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