19 Signal transduction (II)

Question 1

how many domains do G protein coupled receptors have?

Answer 1

3

Question 2

what are the 3 domains of G protein coupled receptors?

Answer 2

• extracellular domain: ligand binding site
• transmembrane domain: 7 Alpha helices
• cytoplasmic domain: G protein binding site

Question 3

What are G protein coupled receptors mediated by?

Answer 3

G proteins (Galpha, Gbeta, Gy subunits)

Question 4

What do G protein use for energy?

Answer 4

GTP, GDP for its activity

Question 5

what is the general pathway of G protein?

Answer 5

0. before ligand binds to receptor, Gα binds with GDP (resting phase)
1. ligand binds to receptor, leading to conformational change of GPCR
2. After ligand binding, Gα releases GDP and binds with GTP for activation.
3. G protein is seperated from receptor. after activation, it dissociates into activated Gα and Gβγ
4. G protein subunits activate or inhibit target proteins. diff Gα isoform= diff outcome of GPCR signaling
5. Gα hydrolyzes GTP to GDP. it becomes inactive
6. inactive Gα binds back with receptor

Question 6

What are the 3 isoforms of Gα?

Answer 6

• Gαs (stimulatory = Gs)
• Gαi (inhibitory = Gi)
• Gαq (=Gq)

outcome is different dependent on the Gα protein

Question 7

What does Gα regulate?

Answer 7

the amount of second messenger of signaling downstream

outcome is different dependent on the Gα protein

Question 8

What is the signaling pathway of Gs?

what happens when Gs is activated?

Answer 8

• once Gs is activated, adenylyl cyclase is activated by phosphorylation
• converts ATP to cyclic AMP (cAMP)
• which activates protein kinase A (PKA) to phosphorylate and activate other proteins

Question 9

What is an example of Gs signaling?

Answer 9

β-adrenergic receptors (β1, β2, β3)

Question 10

How is cAMP produced? and what does it get converted into later?

Answer 10

Activation of adenylyl cyclase converts ATP to cAMP

later cAMP is quickly converted to non-cyclic AMP (5’-AMP)

Question 11

What is the Gi signaling pathway?

Answer 11

opposite of Gs
* has opposite effect to Gs
* once Gs is activated, downstream signaling is inhibited
* cAMP is decreased

Question 12

What is an example of Gi signaling?

Answer 12

α2-adrenergic receptors

Question 13

what is PKA?

Answer 13

protein kinase A

Question 14

Which proteins are targeted by PKA?

Answer 14

myosin light chain kinase (MLCK) leads to muscle contraction
* cAMP inhibits MLCK = cause relaxation of smooth muscle
* activation of β-adrenergic receptors (β1, β2, β3) leads to smooth muscle relaxation

Question 15

What is MLCK and what does it lead to?

Answer 15

myosin light chain kinase (MLCK) leads to muscle contraction

Question 16

what is the Gq protein signaling pathway

Answer 16

1. Ligand binding to G protein coupled receptor activates Gαq
2. Gq activates phospholipase C (PLC)
3. PLC breaks down PIP2 into DAG and IP3
4. DAG activates protein kinase C (PKC)
5. IP3 activates IP3 gated C2+ channel of endoplasmic reiculum
6. Ca2+ is released to activate PKC which phosphorylate and activates other proteins, e.g. those for cell proliferation

Question 17

what is Ca+ important for in smooth muscle?

Answer 17

contraction

Question 18

which hormone is the fight or flight response?

Answer 18

adrenaline (epinephrine)

Question 19

what is an example of Gαq signaling?

Answer 19

α1-adrenoceptor
activation leads to smooth muscle contraction

Question 20

what is the fight or flight hormone?

Answer 20

adrenaline (epinephrine)

Question 21

What happens during fight or flight response?

Answer 21

1. sympathetic nervous system is activated
2. adrenaline (neurotransmitter) is secreted at neuromuscular junctions
3. adrenaline activates adrenergic receptors = smooth muscle contractions

Question 22

What receptor causes smooth muscle contraction and relaxation? and which signaling pathway?

Answer 22

Gq = α1-adrenergic receptor = contraction
Gs = β-adrenergic receptors (β1, β2, β3) = relaxation