Cell signalling 3 Flashcards Preview

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Flashcards in Cell signalling 3 Deck (38)
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1
Q

How is the rod photoreceptor in the vertebrate eye unusual?

A

It is back to front - the receptors for the signal are not on the cell surface and are displayed on membrane stacks - discs of membrane on the outer segment of the cell.

2
Q

What do the discs of photoreceptor in the rods of vertebrate eyes contain?

A

Rhodopsin GPCR.

3
Q

What do the receptors in the rods in the vertebrate eye interact with and what does this interaction result in?

A

Alpha transducin. This is a trimeric G protein. It results in the alpha subunit give up GDP and take up GTP.

4
Q

What is the target protein of alpha-transducin?

A

Cyclic GMP phosphodiesterase. It hydrolyses cyclic GMP to the monophosphate form to remove it from the ion channels at the cell surface.

5
Q

What happens when cyclic AMP is removed from ion channels at the cell surface?

A

The channels close and stops sodium coming into the cell so there is a small membrane potential change that activates neurotransmitters.

6
Q

What does cyclic GMP phosphodiesterase do exactly?

A

It converts cyclic GMP into 5’ GMP.

7
Q

What is unusual about the action of cyclic GMP in the eye rods?

A

It stops the release of inhibitory neurotransmitters rather than promoting neurotransmitter release.

8
Q

What does signal amplification allow?

A

Detection of low light levels for sensitivity.

9
Q

What does adaptation allow?

A

Detection of changes in light levels even in bright light.

10
Q

How is cyclic GMP synthesised from GTP?

A

Guanylyl cyclase.

11
Q

What do mitogens do?

A

Mediate local or short-range communication.

12
Q

What are examples of receptor tyrosine kinase signaling?

A

Insulin-like growth factor, platelet derived growth factor and nerve growth factor.

13
Q

What is tyrosine kinase?

A

An enzyme.

14
Q

What is needed for receptor tyrosine kinase to function and how does this occur?

A

They need to come together as a pair. This is done by interactions with a signal binding to their recognition sites.

15
Q

What happens when receptor tyrosine kinase is activated?

A

There is activation of downstream intracellular signalling pathways.

16
Q

What happens when two copies of receptor tyrosine kinase are brought together?

A

They phosphorylate sites on the other copy of the receptor to activate them and there is a small conformational change.

17
Q

What reverse the signaling of receptor tyrosine kinase?

A

Phsophatase activity.

18
Q

What happens if receptor tyrosine kinase is chronically stimulated?

A

The receptors get internalised and they end up being pinched off into vesicles that fuse with the lysosomes. The signal gets degraded and some of the receptor can go back into the cell surface, but some is destroyed. This can result in a stronger signal needed for a response.

19
Q

What is GEF?

A

Guanine exchange factor.

20
Q

What is Ras?

A

Monomeric GTPase.

21
Q

What is the activity of GTPase promoted by?

A

Interaction with Ras-GAP protein - GTPase activating protein.

22
Q

What happens when receptor tyrosine kinase is activated?

A

It interacts with an adaptor protein that causes Ras-GEF to convert GPD into GTP and then activates the Ras protein, which then causes an onwards transmission of signal.

23
Q

What role does the adaptor protein have in the tyrosine kinase pathway?

A

It interacts with the target protein and brings free Ras-GEP to the correct place to interact with the inactive Ras protein.

24
Q

What is the reversal step involved in the receptor tyrosine kinase pathway?

A

The active Ras proteins are self-inactivated.

25
Q

What does Ras stimulate?

A

A serine/threonine kinase cascade.

26
Q

What are the kinases that active Ras protein activates?

A

Activated MAP kinase kinase kinase, activated MAP kinase kinase and activated MAP kinase.

27
Q

What does MAP mean?

A

Mitogen-activated kinases.

28
Q

How can the sensitivity of the kinase/serine/threonine cascade be increased?

A

The signal is amplified in each step, and allows proteins to interact that might be activated by different signalling systems.

29
Q

How do receptor tyrosine kinases stimulate cell survival?

A

They activate PI3-kinase to change its conformation.

30
Q

What are the key targets in the receptor tyrosine kinase pathway to stimulate cell survival?

A

Protein kinase 1, protein kinase 2 and Akt.

31
Q

What does Akt do?

A

It inactivates BAD to prevent cell death.

32
Q

What does BAD do?

A

It activates Bcl2 due to phosphorylation of BAD, which inhibits apoptosis.

33
Q

What else can Akt activate?

A

mTOR which inhibits protein degradation and stimulates protein synthesis, resulting in cell growth.

34
Q

What is the Ras/MAP-kinase pathway so important?

A

It often promotes cell proliferation, Ras neutralizing antibodies can block cell proliferation, the Ras gene is mutated in 30% of human cancers and other members of the pathway are oncogenes and tumour suppressors.

35
Q

What does protein conformation changes allow?

A

They are frequently used in signalling pathways and allow switching between active and inactive states.

36
Q

What proteins are involved in conformational changes due to phosphorylation?

A

Protein kinase and protein phosphatase.

37
Q

What molecules are involved in conformational changes in GTP-binding protein?

A

GTP binding and GTP hydrolysis.

38
Q

What might need to happen in order to get a full response from a cell?

A

There may need to be cross-talk of multiple systems.