Signal Transduction Flashcards
State the function of second messengers
Mediate cell activity - inside the cell
What do signalling proteins act as ?
Molecular switches
State the 2 ways to activate/deactivate signalling proteins
Signalling by phosphorylation
Signalling by GTP binding
What does the human genome encode ?
520 kinases
150 phosphatases
Function of kinase
Unphosphorylated protein - OFF protein
Kinase uses ATP to phosphorylate protein which will change the chemistry of the protein and put it in an ON position.
How does the signalling protein return to its OFF position ?
Cleavage of the phosphate group by another type of enzyme called a phosphatase.
Commonly used mechanism for switching on and off proteins.
Describe the use of GDP and GTP in cell signalling
In OFF position, the proteins will have GDP bound.
Some sort of change in behaviour occurs, such that GDP no longer binds, and its affinity for GTP increases.
GTP binds instead, giving rise to a different structure putting it in the ON position.
State the 2 types of GTP-binding proteins
Trimetric G proteins
Monometric GTPases
Trimeric G proteins
Associated with G protein coupled receptors
State the 2 main types of kinase
Tyrosine kinase
Serine/Threonine Kinase
Describe G-protein coupled receptors
These receptors are coupled to the G proteins, which are hetrotrimeric
These G proteins can open ion channels / activate enzymes which produce second messenger molecules.
Second messenger molecules mediate cellular effects.
Describe how G-protein coupled receptors work
Ligand binding activates a G-protein which in turn activates or inhibits another protein.
Often this is an enzyme that generates a specific second messenger.
What happens when a ligand binds to the G protein coupled receptor ?
Ligand binding to a G protein coupled receptor activates the associated G protein which in turn inhibits / activates a downstream enzyme to generate an intracellular second message.
Describe the structure of G protein coupled receptors
7 membrane spanning regions (alpha helixes) with their amino termini on the extracellular face and their carboy termini on the cytoplasmic face of the plasma membrane.
Describe the intracellular G protein coupled receptor loops
Many cell-surface receptors are coupled to trimeric signal-transducing G proteins that bind either GTP or GDP.
Trimeric
Composed of 3 different subunits (alpha, beta and gamma)
Describe the mechanism of action of G proteins
Binding of the ligand to the receptor changes its conformation, causing it to bind the G alpha protein in such a way that GDP is displaced and GTP is bound.
This triggers G beta/gamma dissociation activating downstream pathways.
Activation is short-lived, as GTP bound to G alpha hydrolyses to GDP in seconds, leading to the reassociation of G alpha with G beta/gamma and inactivation of adenylate cyclase.
Function of GTP
GTP is required for the ligand-induced stimulation of adenylate cyclase.
Glucagon receptor couples to G alpha
What does the Martin Rodbell experiment require ?
A receptor (glucagon)
A transducer (G-protein)
An amplifier (adenylate cyclase - generates large amounts of a second messenger)
Second messenger is cAMP