2nd Messengers

Question 1

What are the properties of second messengers?

Answer 1

• Amplify the effects of a cell signal

- Easily difusable across the cytosol

Question 2

Name 4 second messengers

Answer 2

1. Cyclic AMP
2. IP3
3. DAG
4. Calcium

Question 3

What is the function of a molecular switch?

Answer 3

Allows the switching on/off of molecular pathways

e.g protein phosphorylation/GTPase

Question 4

What effects does an increase in cAMP have on:

a) the liver
b) ovarian follicle
c) cardiac muscle

Answer 4

a) Increased conversion of glycogen to glucose
b) Increased estrogen/progestrogen
c) Increased contraction

Question 5

How are the 2nd messengers DAG and IP3 produced?

Answer 5

• Both derived from lipid phosphoinositol (PI) which can be reversibly phosphorylated
• Its derivative PiP2 (4,5-biphosphate) can go on to produce 1,2 - diaglycerol (DAG) and 1,4,5 - triphosphate (IP3) when cleaved by phospholipase C-B

Question 6

Where are DAG and IP3 found and what are their major functions?

Answer 6

DAG - Remains attached to membrane, activates protein kinase C to regulate cell function
IP3 - Found in cytosol, releases Ca2+ from the endoplasmic reticulum

Question 7

How does IP3 mediate Ca2+ release?

Answer 7

• Activation of phospholipase C cases cleavage

- Ip3 binds to receptors on the ER to open Ca2+ channels

Question 8

How does DAG activate protein kinase C (PKC)?

Answer 8

• Receptor activation causes IP3 to release Ca2+ into the cytosol
• Ca 2+ recruits PKC to the membrane via the protein RACK which it binds to
• Ca2+ and DAG bind to the regulatory subunit of PKC activating it and allowing it to phosphorylate targets on the plasma membrane
  note: G protein coupled receptor usually activates phospholipase C for cleavage

Question 9

What accessory protein does Ca2+ often work with?

Answer 9

Calmodulin - bonds to 4 Ca2+ ions causing a conformational change to its C-shaped structure allowing it to wrap around the target site of a protein

Question 10

Describe the process of activation of calmodulin-dependent kinase

Answer 10

When inactive - inhibitory domain blocks catalytic domain

• Upon increase of intracellular Ca2+ calmodulin is activated and binds to inhibitory domain causing CaMKII to be activated
• For complete activation catalytic domain autophosphorylates the regulatory domain
• Pathway dependent on how it is activated and for how long

Question 11

Describe the method of deactivation of CaMKII

Answer 11

• Activity drops when Ca2+ decreases

- Complete inactivation only when protein phosphatase takes phosphate group off regulatory group

Question 12

Name 4 targets of CamKII

Answer 12

Calcineurin - phosphatase responsible for the regulation of transcription factors
CREB - transcription factor responsible for many neuropeptides
GSK3 - major regulator of cell metabolism, cell proliferation and apoptosis
AMPA / NMDA receptors - regulators of synaptic pasticity