Receptor Signalling

Question 1

Three stages of cell signalling

Answer 1

1. Reception
2. Transduction
3. Response

Question 2

Heterotrimeric G proteins

Answer 2

Contains alpha, beta and gamma subunits

G-alpha-i: inhibition of cAMP production
G-alpha-s: increase cAMP production
G-alpha-q: increase DAG and IP3 production
G-alpha-12/13: activates Rho

Question 3

Signal amplification

Answer 3

500 G-proteins activated –> 100000 cGMP hydrolysed –> 500 cGMP phosphodiesterase activated —> 250 sodium channels close –> 10^6-10^7 ions don’t enter the cell –> membrane potential altered by 1mV –> signal travels to brain

Question 4

G-alpha-s signalling

Answer 4

Activating G-alpha-s coupled receptors leads to production of the second messenger cAMP, cAMP activates protein kinase A (PKA)

In presence of agonist, GDP dissociates from G-protein and GTP binds. The alpha-s subunit binds (???) to the adenylate cyclase enzyme, causing ATP to be converted to cAMP, activating PKA.

Question 5

G-alpha-i signalling

Answer 5

Activating G-alpha-i coupled receptors leads to a reduction in the production of the second messenger cAMP.

G-alpha-i subunit still binds (???) to adenylate cyclase but inactivates it (???) reeducing production of cAMP.

Question 6

G-alpha-q signalling

Answer 6

Activating G-alpha-q coupled receptors leads to increased intracellular calcium. The calcium is released from the ER by the second messenger inositol triphosphate (IP3).

GDP dissociated from alpha-q subunit, GTP binds, alpha-q subunit binds to phosppholipase C which causes IP3 to be produced from PIP2. IP3 binds to calcium channels, causing the release of Ca2+ from the ER. IP3 also activates (???) DAG resulting in PKC activation.

Question 7

Second messengers

Answer 7

Cyclic nucleotides: cAMP, cGMP
Phospholipids: PIP2, IP3, DAG
Ions: Ca2+
Gases: NO

Question 8

Second messenger: calcium

Answer 8

Causes:

• contraction of muscle
• release of neurotransmitter
• cell proliferation and migration
• secretion of hormones
• regulates gene expression

Question 9

From cAMP to glucose

Answer 9

Reception:
- Adrenaline binds to G-protein linked receptor

Transduction:

• Inactive G protein –> active G protein
• Inactive adenylyl cyclase –> active adenylyl cyclase
• ATP –> cyclic AMP
• Inactive protein kinase A –> active protein kinase A
• Inactive phosphorylase kinase –> active phophorylase kinase
• Inactive glycogen phophorylase –> active glycogen phosphorylase

Response:
- Glycogen –> glucose-1 phosphate

Question 10

Receptor Tyrosine Kinase signalling

Answer 10

Hormone binds to receptor, activating it, leading to dimerisation, resulting in autophophorylation of thr v-terminus of each receptor. This allows other protein to bind and initiate a kinase cascade.