2004B15 Describe the mechanism of action of G-proteins in the cell.



·         Diagramme

·         G protein

·         G protein subtypes




G protein:


·   Heterotrimeric ICF protein

·   α, β, γ subunits


·   Transduces signal from ECF to ICF

·   Amplifies signal 100x

·   Self-inactivates

·   Unidirectional

·   Metabotropic effects

·   Cell-dependent effects

Time course

·   Onset: seconds to minutes

·   Duration: minutes

o Longer than ligand binding

o Longer than plasma half life may predict (e.g. adrenaline)

Mechanism of tolerance

·   ICF carboxyl terminal is phosphorylated

·   β-arrestin binds

·   Receptor is downregulated and destroyed


G protein subtypes:


·   e.g. adrenaline at β1

·   α-GTP stimulates adenylyl cyclase activity -> ↑cAMP -> ↑protein kinase activity


·   e.g. morphine at μ opioid receptor

·   α-GTP inhibits adenylyl cyclase -> ↓cAMP -> ↓protein kinase activity


·   e.g. vasopressin at V1R

·   α-GTP activates PLC

·   PLC cleaves PIP2 into IP3 and DAG

·   IP3 -> ↑ ICF [Ca2+]

·   DAG activates PKC

Small G protein

·   Same as α-subunit of heterotrimeric G proteins

·   Free in ICF

·   Hydrolyses GTP

·   Role in gene expression, cytoskeletal function etc.




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