Cell signalling 3

Question 1

How is the rod photoreceptor in the vertebrate eye unusual?

Answer 1

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.

Question 2

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

Answer 2

Rhodopsin GPCR.

Question 3

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

Answer 3

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

Question 4

What is the target protein of alpha-transducin?

Answer 4

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

Question 5

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

Answer 5

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

Question 6

What does cyclic GMP phosphodiesterase do exactly?

Answer 6

It converts cyclic GMP into 5’ GMP.

Question 7

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

Answer 7

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

Question 8

What does signal amplification allow?

Answer 8

Detection of low light levels for sensitivity.

Question 9

What does adaptation allow?

Answer 9

Detection of changes in light levels even in bright light.

Question 10

How is cyclic GMP synthesised from GTP?

Answer 10

Guanylyl cyclase.

Question 11

What do mitogens do?

Answer 11

Mediate local or short-range communication.

Question 12

What are examples of receptor tyrosine kinase signaling?

Answer 12

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

Question 13

What is tyrosine kinase?

Answer 13

An enzyme.

Question 14

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

Answer 14

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

Question 15

What happens when receptor tyrosine kinase is activated?

Answer 15

There is activation of downstream intracellular signalling pathways.

Question 16

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

Answer 16

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

Question 17

What reverse the signaling of receptor tyrosine kinase?

Answer 17

Phsophatase activity.

Question 18

What happens if receptor tyrosine kinase is chronically stimulated?

Answer 18

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.

Question 19

What is GEF?

Answer 19

Guanine exchange factor.

Question 20

What is Ras?

Answer 20

Monomeric GTPase.

Question 21

What is the activity of GTPase promoted by?

Answer 21

Interaction with Ras-GAP protein - GTPase activating protein.

Question 22

What happens when receptor tyrosine kinase is activated?

Answer 22

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.

Question 23

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

Answer 23

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

Question 24

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

Answer 24

The active Ras proteins are self-inactivated.

Question 25

What does Ras stimulate?

Answer 25

A serine/threonine kinase cascade.

Question 26

What are the kinases that active Ras protein activates?

Answer 26

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

Question 27

What does MAP mean?

Answer 27

Mitogen-activated kinases.

Question 28

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

Answer 28

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

Question 29

How do receptor tyrosine kinases stimulate cell survival?

Answer 29

They activate PI3-kinase to change its conformation.

Question 30

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

Answer 30

Protein kinase 1, protein kinase 2 and Akt.

Question 31

What does Akt do?

Answer 31

It inactivates BAD to prevent cell death.

Question 32

What does BAD do?

Answer 32

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

Question 33

What else can Akt activate?

Answer 33

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

Question 34

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

Answer 34

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.

Question 35

What does protein conformation changes allow?

Answer 35

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

Question 36

What proteins are involved in conformational changes due to phosphorylation?

Answer 36

Protein kinase and protein phosphatase.

Question 37

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

Answer 37

GTP binding and GTP hydrolysis.

Question 38

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

Answer 38

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