Signalling via Heterotrimeric G-Proteins Flashcards
What are the TWO major groups of Signalling G-Proteins?
- Monomeric Ras G-protein
- Heterotrimeric G-protein
Which G-proteins do signalling molecules act via to increase the levels of secondary messengers?
Heterotrimeric G-proteins
What is the mechanism of action for signalling via G-proteins?
- G-protein binds GTP or GDP
- Transduce hormone / neurotransmitter signals
- G-proteins couple signals to secondary messengers
How is GTP converted to GDP on G-proteins?
By hydrolysis of the gamma phosphate of GTP
What is the mechanism of action of signal transduction via heterotrimeric G-proteins?
- Hormone binding causes conformational change in receptor
- Receptor binds α subunit of G-protein (GDP bound state)
- Binding of receptor causes conformational change in α subunit (GTP replaces GDP)
- α dissociates from β and γ and binds adenylyl cyclase
- Synthesis of cAMP activated
- Hormone dissociates
- GTP hydrolysed to GDP
- α binds β and γ again
What is the function of Gαs?
Alpha subunit which activates adenylyl cyclase
How many isoforms of Gαs are there?
3
Which ligands activate Gαs?
Stimulatory ligands such as Adrenaline and Glucagon
What is the function of Gαi?
Prevents adenylyl cyclase activation
Which ligands activate Gαi?
Activated by inhibitory ligands such as Adenosine
How many members does Gαi contain?
At least 9
What is the function of Gαq?
Activate phospholipase C that increases DAG and IP3
How many isoforms does Gαq have?
5
How many members does Gα12 have?
2
TRUE OR FALSE:
Different Gα subunits couple different GPCRs
True
What is the function of the secondary messenger cAMP in the G-protein signalling pathway?
Activates Protein Kinase A (PKA)
What is the function of the secondary messenger cGMP in the G-protein signalling pathway?
Activates Protein Kinase G (PKG) and opens cation channels in rod cells
What is the function of the secondary messenger DAG in the G-protein signalling pathway?
Activates Protein Kinase C (PKC)
What is the function of the secondary messenger IP3 in the G-protein signalling pathway?
Opens Ca2+ channels in the ER
TRUE OR FALSE:
The Gα subunit does not have GTPase activity
False.
Gα subunit HAS intrinsic GTPase activity which allows the hydrolysis of GTP to GDP
What TWO ways can G-protein coupled responses be decreased by desensitisation?
- Receptor internalisation
- Phosphorylation of the receptor by GCPR kinases (GRKs)
How does Cholera toxin affect Gαs G-proteins?
- Irreversibly activates Gαs G-proteins by ADP-ribosylation
- Leads to an excessive, non-regulated elevation in cellular cAMP levels
How does Pertussis toxin affect Gαi G-proteins?
- ADP-ribosylates Gαi
- Permanently locks G-protein into the GDP-bound state (removes inhibitory action)
- Leads to an increase in cAMP levels
What is the function of the βγ subunits of G-proteins?
Regulate plasma membrane K+ channels