W7 - Enzyme Coupled Receptors Flashcards
What are the different types of receptor
G protein coupled receptor
Ligand gate ion channel
Enzyme coupled receptor
Nuclear receptor
What is the notation for an Enzyme Coupled Receptor
ECR
What are ECR’s linked too
They are often linked to an enzyme activity
What are the six classes of ECR
Receptor tyrosine kinases
Tyrosine Kinase associated receptors
Receptor serine/threonine kinases
Histidine -Kinase - associated receptors
Receptor guanylyl cyclases
Receptor like tyrosine phosphatases
What do Receptor tyrosine kinases phosphorylate on
Phosphorylate tyrosine residues on a specific set of substrates, usually activated by growth factors and or hormones
What examples of receptor tyrosine kinases affect cellular proliferation
Epidermal growth factor
Platelet derived growth factor
Vascular endothelial growth factor
How are signals transduced across the plasma membrane
Most ECRs are single alpha helices, Dimerization or oligomerization occurs of the receptors subunits.
This is often caused by ligands before the ligand binding.
Oligomerization causes reorientation so changes the shape of the protein inside the cell.
This then induces signaling and phosphorylates itself (autophosphorylation)
How does autophosphorylation work
Agonist binds to the receptor which dimerizes
within the cell there are intracellular kinase domain which function as phosphorylation enzymes.
When the domains come together from dimerization atp adds phosphate to tyrosine residues leaving adp.
This leads to increase in tyrosine kinase activity
How does autophosphorylation provide a biological effect
Once the tyrosine residues have been phosphorylated via autophosphorylation
they will go down the chain and phosphorylate other tyrosine residues
which bind with intracellular signalling proteins getting a formation of signalling complexes.
Describe how a signal is generated by the epidermal growth factor (example of a ECR)
Dissociation of 2 proteins
○ GRB2
○ SOS
Activates membrane tethered raz protein
Exchange of gdp for gtp
This then passes to Raf1
Raf 1 phosphorylates Mek
Mek phosphorylates ERK
ERK goes about its function
What does a phosphorylation cascade require
Atp and phosphate
What does ERK do once it is phosphorylated
Once it is phosphorylated by Mek
it translocates into the nucleus where it activates something known as c-FOS via phosphorylation.
C-Fos then binds to the DNA and induce transcription of different genes such as AP-1 ELK-1
What do insulin receptors exist as
- They exist as tetramers linked via disulphide bridges, so 4 polypeptide chains linked together
Describe what happens when insulin binds to the insulin receptor
Insulin binds to the receptor
Reordering of the intracellular kinase domains
Autophosphorylation and activation of signalling cascades
Binds IRS-1 and PI3K together
PI3K phosphorlyates pip2 to pip 3
This then activates a phosphorylation cascade leading to glycogen synthase producing glycogen
At one part there is AKT which translocates glucose transporters
Uptakes glucose from the blood
Why do we need to understand the molecular signalling pathways
- By identifying molecules involved in signaling may unearth new targets for drugs
