Week 4 - Cell Signalling Flashcards

1
Q

What is Herceptin’s target

A

HER2

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2
Q

What is salbutamol’s target

A

Cell surface receptor (beta 2 receptor)

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3
Q

What is imatinib’s target (used to treat CML)

A

Intracellular protein tyrosine kinase (Bcr-Abl)

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4
Q

What is bevacizumab’s target

A

VEGF which is the signal for angiogenesis

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5
Q

In which 2 ways can biochemical signals be classified

A

Chemical structure and range of action (distance)

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6
Q

Why is cell signalling important?
(3)

A

To coordinate development

To maintain normal physiological function

If signalling is abnormal, it can cause disease

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7
Q

3 types of signalling molecules

A

Amino acid derivatives
-Adrenaline (modified aa)
- Oxytocin (peptide hormone)
- Insulin (insulin, growth hormone)

Steroid hormones (derived from cholesterol)
- Testosterone

Eicosanoids (derived from lipids)
e.g prostaglandin

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8
Q

What is the name for long distance chemical signalling

A

Endocrine - via blood

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9
Q

What is the name for chemical signalling between nearby cells

A

Paracrine

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10
Q

What is the name for chemical signalling via cell:cell contact

A

Juxtacrine

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11
Q

What is the name for chemical signalling from the same cell

A

Autocrine

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12
Q

What are the 3 stages of signal transduction

A

Detection

Transduction

Response

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13
Q

How do hydrophobic signal molecules reach their receptor

A

Through the membrane as they are hydrophobic

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14
Q

Examples of hydrophobic signalling molecules

A

Steroid hormones - oestrogen/testosterone
Nitric acid (g)

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15
Q

What is the steroid hormone’s mechanism of action

A

Steroid hormone diffuses through the membrane and binds directly to the intracellular receptor proteins

The hormone-receptor complex acts as a transcription factor which binds to DNA and alters gene expression

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16
Q

Example of a hydrophobic signalling molecule

A

Steroid hormone

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17
Q

Example of a hydrophilic signalling molecule

A

Insulin/adrenaline

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18
Q

What must hydrophilic signalling molecules use to cause a response

A

They must use a cell surface receptor protein

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19
Q

What are the 3 main types of cell surface receptors and give an example

A

Ion-channel-linked
(glutamate neurotransmitter)

G-protein-linked (GPCR)
(adrenaline, serotonin)

Enzyme-linked
(RTK, growth factors, insulin)

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20
Q

Describe the mechanism of an ion-channel-linked receptor

A

Signal molecule binds to receptor on receptor. Ion flow into cell changes electrical properties of the cell

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21
Q

Describe the mechanism of a G-protein-linked/coupled (GPCR)

A

Signal molecule binds to activated G protein which then activates enzyme that passes on signal into cell

22
Q

Describe the mechanism of the enzyme-linked receptor

A

Signal molecule binds to receptor, bringing the receptor together (dimerisation) which then goes on to activate an intracellular enzyme

23
Q

Which enzyme phosphorylates molecules

A

Kinase

24
Q

Which enzyme dephosphorylates molecules

A

Dephosphatase

25
Q

Outline the mechanism of the enzyme-linked receptor RTK (receptor tyrosine kinase)

A

Signalling molecule binds to receptor, receptor is pulled closer together, dimerisation occurs. Tyrosine is phosphorylated by kinase, which act as a docking station for intracellular proteins

26
Q

Two methods of transduction

A

Enzyme cascades

Second messengers

27
Q

When are MAPK cascades often activated

A

In response to RTK activation by growth factors (receptor tyrosine kinases) e.g EGF

28
Q

What type of cascade is an MAPK

A

An enzyme cascade

29
Q

What is often activated in response to growth factor RTK activation e.g by EGF

A

MAPK cascades

30
Q

What happens before an MAPK cascade after phosphorylation of tyrosine occurs

A

Relay proteins such as Grb/Sos activate the proto oncogene RAS

MAP kinase cascade is activated

Signal is amplified

31
Q

What is a second messenger

A

Small molecule produced in large amounts inside the cell after receptor activation

32
Q

Give an example of a second messenger

A

cAMP

33
Q

How do second messengers result in cellular response

A

Signal molecule binds, G protein is activated and activates the
Enzyme. Enzyme converts ATP into lots of cAMP. cAMP binds to
Molecule callsed protein kinase A and activates it. The kinase
Can then be used to phosphorylate lots of different target proteins.

34
Q

Name 3 other second messengers other than cAMP

A

DAG which activates PKA

IP3 which causes Ca2+ release
Ca2+ which activates Ca-dependent enzymes including CaMKs

35
Q

What is the typical pairings of GPCRs/RTKs and second messengers/MAPK

A

GPCRs usually activate second messengers

RTKs usually activate MAPK cascades

36
Q

Name 4 different responses possible as a result of signal molecule reception and transduction

A

Gene expression

Protein activity

Protein binding

Protein localisation

37
Q

What do drugs ending in AB do

A

Use antibodies to inactivate them and block the signalling pathway

38
Q

What do drugs ending in IB do

A

They use small molecule kinase inhibitors to block the signal pathway

39
Q

Which pathways are usually overactive in cancer

A

Growth factor

Receptor Tyrosine Kinase

40
Q

What does herceptin target

A

It targets the factors that produce the human epidermal growth receptor

41
Q

What does Bevacizumab target

A

VEGF (vascular endothelial GF) which prevents angiogenesis

42
Q

What does Gefitinib target

A

Iti inhibits EGFR receptor (lung cancer)

43
Q

When G protein is active, which nucleotide is bound to alpha subunit

A

GTP

44
Q

When G protein is inactive, which nucleotide is bound to alpha subunit

A

GDP

45
Q

How is G protein deactivated

A

GAP protein hydrolyses G protein into GDP

46
Q

Effector proteins produced as a result of activated G protein can do what

A

Can activate or inhibit targets, directly or indirectly

47
Q

During glucose release caused by adrenaline, what are the two pathways that can result from phosphorylated kinase activator

A

Activation of kinase which phosphorylase glycogen into glucose

OR

Activation of glycogen synthase which phosphorylase glycogen synthase which de phosphorylases glucose into glycogen

48
Q

What happens when adrenaline no longer binds to receptor, this triggers what?

A

This causes the G protein subunit to no longer be activated. Phosphodiesterase removes the residual cAMP

49
Q

Can signalling molecules activate singular pathways or multiple

A

They can activate multiple!

50
Q

How is specificity in signalling achieved?

A

The factors that contribute to variation are:

The type of receptor

The G protein involved

The effector enzyme

The second messenger produced

51
Q

Why shouldn’t you give a patient with heart problems beta blockers if they also have asthma?

A

you don’t want to give a patient with heart condition AND asthma beta blockers because it will have an antagonistic effect on bronchodilation!

52
Q
A