Signal Transduction Flashcards
What is the equation for the Therapeutic index of a drug?
Maximum non-toxic dose divided by Minimum effective dose
What are the key features of the nicotinic ACh receptor?
- It is a LGIC comprised of 5 subunits.
- The two alpha subunits are the binding points of the ACh
- Two ACh molecules are required to activate the receptor
What are the key features of the AMPA (glutamate) Receptor?
- It is tetrameric
- Its activation results in an excitatory response
What are the three classes of Single Transmembrane receptors?
1) Receptor Tyrosine Kinases
2) Serine Threonine Kinases
3) Cytokine Receptors
What are the key features of GPCR’s?
They are coupled to a heterotrimeric G protein. The alpha sub unit binds the G protein and also has GTPase activity
Name the four main types of G protein and their effect within a cell.
Gs- stimulates AC, increases cAMP, activates PKA, opens Ca channels
Gi- inhibits AC, decreases cAMP, opens K channels
Gq/11- stimulates PLC Beta, increases IP3, DAG and Ca. DAG activates PKC which opens K channels
Go- stimulates PLC-Beta which activates K channels.
What are the key features of Receptor Tyrosine Kinase activation?
- most RTKs are single subunit proteins, they dimerise upon ligand binding
- Auto-phosphorylation of Tyrosine residues produces SH2 homology domains
What are the 5 steps involved following activation of the Epidermal Growth Factor RTK?
1) Grb-2 binds to SH2 domains on receptor
2) SOS binds to Grb-2
3) SOS exchanges GDP to GTP on Ras
4) Ras-GTP activates Raf kinase
5) Raf kinase phosphorylates MAPKK
What are the 5 steps involved in signal transduction following activation of the Insulin receptor?
1) IRS-1 is phosphorylated upon binding to the receptor
2) PI-3 Kinase binds to phosphorylated IRS-1
3) activated PI-3K phosphorylates PIP2 making PIP3
4) PDK1 and PKB bind to PIP3 (SH3 domain)
5) PDK1 phosphorylates PKB
