Cell signalling 3

Question 1

What does Raf use to phosphorylate and activate Mek?

Answer 1

ATP

Question 2

What does activated Mek do?

Answer 2

It phosphorylates and activated Erk

Question 3

What does Mek use to phosphorylate and activate Erk?

Answer 3

ATP

Question 4

What can activated Erk do?

Answer 4

Phosphorylate, and thus activate different proteins and transcription factors

Question 5

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

Answer 5

Promote cell proliferation

Question 6

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

Answer 6

Each kinase can activate multiple kinases etc etc

Question 7

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

Answer 7

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

Question 8

What is an oncogene?

Answer 8

A muated gene that has the potential to cause cancer

Question 9

What is a proto-oncogene?

Answer 9

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

Question 10

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

Answer 10

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

Question 11

How is phosphorylation status a signalling switch?

Answer 11

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

Question 12

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

Answer 12

Protein phosphotase

Question 13

Where does PI3kinase bind to in the PI3K pathway?

Answer 13

The phosphotyrosine onto HER3

Question 14

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

Answer 14

It is activated

Question 15

What type of kinase is PI3K?

Answer 15

A lipid kinase

Question 16

What does PI3K uses PIP2 for?

Answer 16

As a substrate to generate PIP3

Question 17

Where are PIP2 and PIP3 found?

Answer 17

Membrane bound

Question 18

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

Answer 18

High affinity binding to PIPs

Question 19

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

Answer 19

Pleckstrin Homology Domains

Question 20

What do Protein kinase 1 and Akt use PIP3 as?

Answer 20

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

Question 21

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

Answer 21

It phosphorylates, and activates it

Question 22

What does Akt do immediately after being phosphorylated?

Answer 22

It dissociates from the PIP and the plasma membrane

Question 23

What process is Akt important in?

Answer 23

Cell survival

Question 24

What is active Akt?

Answer 24

A serine/threonine kinase

Question 25

What does active Akt do to Bad?

Answer 25

Akt phosphorylates Bad

Question 26

What does Bad do in its active form?

Answer 26

It holds Bcl2 in its inactive state

Question 27

What does the phosphorylation of Bad do?

Answer 27

Changes Bad’s conformation, causing it to release Bcl2

Question 28

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

Answer 28

Activates it

Question 29

What is the role of active Bcl2

Answer 29

Promotion of cell survival by inhibition of apoptosis

Question 30

How does active Akt mediate cell growth?

Answer 30

Through other signalling events, it ends up activating mTor

Question 31

What does mTor do once activated?

Answer 31

Inhibits protein degradation and stimulates protein synthesis

Question 32

Where does phospholipase C gamma bind to?

Answer 32

A phosphotyrosine of HER3

Question 33

What does phospholipase C gamma use PIP2 for?

Answer 33

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

Question 34

Where is IP3 sent after it is generated?

Answer 34

To the cytosol

Question 35

What does IP3 do once it is in the cytosol?

Answer 35

It binds to, and opens calcium channels in the ER

Question 36

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

Answer 36

The cytosolic concentration of Ca2+ increases

Question 37

What does DAG do once generated?

Answer 37

Recruits and activates protein kinase C (PKC)

Question 38

What can cytosolic ca2+ bind to?

Answer 38

PKC