Signal Transduction Flashcards
What is signal transduction?
Where a receptor on the cell surface binds to an extracellular signalling molecule, causing a change in conformation which causes a pathway of events leading up to a cellular response.
What are the names of the three receptor ‘superfamilies’?
G-protein coupled receptors
Ligand gated ion channels
Receptors with intrinsic enzyme activity
What are the two types of G-protein coupled drugs and how do they work? Examples.
Agonists - bind to receptors and ACTIVATE them e.g. Salbutamol (asthma)
Antagonists - bind to receptor and BLOCK them e.g. Propranolol (hypertension)
Describe the structure of a GPCR.
Consists of 7 transmembrane regions (7TM) with an extracellular N terminal and an intracellular C terminal.
A ligand binding site can be made up of X or Y.
X = 2-3 transmembrane domains Y = on the N terminal
What effect does PTx (Pertussis toxin) have on a GPCR?
PTx affects a specific Gi protein. It inhibits GDP to GTP conversion, meaning the cell can’t turn ‘on’.
What effect does CTx (Cholera Toxin) have on the cell?
affect alpha s proteins. After the alpha and beta/gamma subunits have disassociated and triggered their effectors, CTx inhibits GTPase conversion back to GDP, meaning the cell is in a permanent ‘on’ state (for hours rather than mins) - causes cell degradation.
Effectors can be X or Y.
X = Enzymes e.g. Adenyly cyclase Y = Ion channels e.g. Voltage operated Ca2+ channels (VOCC)
What is the full name of a G protein?
Guanine-nucleotide binding protein
What is a heterotrimeric complex?
Consists of 3 subunits, alpha, beta and gamma, which make up 2 parts, alpha and beta/gamma.
What process in undergone when a G protein is activated which causes an effector?
When the GPCR receptor is activated, is causes the release of the GDP molecule attached to the alpha subunit and the binding of GTP in its place. This causes the alpha and beta/gamma subunits to disassociate, where they separately interact with an specific effector.
How do the disassociated alpha and beta/gamma sub units rejoin?
GTPase in undergone which hydrolyses GTP back to GDP with the addition of a phosphate molecule. Here, the subunits reassociate and the heterotrimeric complex is complete, turning the response ‘off’.
Explain how signal transduction plays a role in the regulation of adenylyl cyclase.
An agonist binds to the receptor, causes a Gs signal activation and the alpha and beta/gamma subunits split. The remaining alpha subunit changes the activity of adenylyl cyclase in the plasma membrane, where ATP creates a second messenger cyclic AMP, which interacts with the cyclic AMP dependant protein kinase (PKA) in the cytoplasm.
Name 3 receptors that would activate the adenylyl cyclase pathway.
Beta - adrenoceptors
D1 - dopamine receptors
H2 - Histamine receptors
All these activate Gs proteins
Describe the affect inhibitors can have on the adenylyl cyclase pathway.
Inhibitors affect the Gi proteins in the pathway. They inhibit the production of the second messenger cyclic AMP (ATP to cyclic AMP) therefore the enzyme pathway cannot continue.
