M&R Session 7- Effector Mechanisms In Intracellular Signalling Flashcards
Which G proteins stimulate and inhibit adenylyl cyclase?
Stimulate- Gs
Inhibit- Gi
Effectors can be…
Enzymes or ion channels
What does adenylyl cyclase do?
Convert ATP to cyclic AMP which is a secondary messenger and activates the enzyme cyclic AMP-dependent protein kinase.
How does the binding of cyclic AMP activate Cyclic AMP-dependent protein kinase?
It’s attachment causes the dissociation of the catalytic subunits to detach from the regulatory subunits of the enzyme and consequently expose their active sites, allowing the catalytic components to phosphorylate target proteins.
What does phospholipase C act on and what are the products?
PIP2
DAG and IP3.
What does IP3 do?
Acts on IP3 receptors of the ER and stimulates calcium release into the cytoplasm.
Activates protein kinase C along with DAG.
Which amino acids of target proteins do protein kinases interact with?
Serine and threonine
Why is signal amplification necessary?
For an extracellular signal to generate an intracellular response.
Outline the amplification pathway
- activated receptor can cause GDP/GTP exchange on more than one G protein
- activated G proteins can activate multiple effector molecules
- effector molecules act catalytically.
Which G protein activates adenylyl cyclase?
Gs
Which G protein inhibits adenylyl cyclase?
Gi
Which G protein activates cyclic GMP phosphodiesterase in visual excitation?
Gt
Which G protein activates K+ channels?
Gi
What are the five methods of deactivation of GPCR pathways?
- Once receptor has interacted with a G protein, the affinity for the agonist is reduced, meaning dissociation is likely.
- Whilst activated, the receptor is prone to phosphorylation by a variety of protein kinases. This would prevent it activating another G protein.
- Active lifetime of GTP may be limited by cellular factors that activate intrinsic GTPase in G alpha subunit.
- Enzymatic activities in the cell are such that the basal state is favoured and so returned there as quickly as possible.
- Enzymatic cascades activated downstream of PKs act to oppose their effect.