BIOL 2020 Lecture Notes - Lecture 12: Second Messenger System, Hydrolysis, Stat Protein
Cell Signal Transduction: Communication Between Cells
Summary
o Lipids have properties that allow them to signal
o Phosphatidylinositol derived second messengers
Signaling Pathways- General Features
o The first thing needed is a signal, there is a molecule secreted by another cell that is
released outside of the cell
o It can be released very close to the cell (ex. Neurotransmission)
o It can also be very far away, such as a gland that releases a hormone. That hormone
has to travel throughout the blood stream and will get diluted, but the signal is
amplified within the right cell regardless
o The idea is that in EVERY case, a receptor is needed
o Transmembrane receptors
o Know that there are a possibility of signals that are able to just cross the membrane,
they are still picked up by a receptor, but this receptor is inside the cell
o Examples of these are hormones and steroids
o First messenger (ligand) is the extracellular signal
o The first messenger to bind to the receptor and cause a change in conformation of the
receptor, which then causes a change on the other side of the membrane
o It will activate an enzyme called an effector - it's intermediate is a G protein
o The activation of an effector releases/produces a second messenger
o Second messenger is a small molecule and in response to a signal receptor that activates an
effector, a lot of second messenger can be produced, thus there is a large potential for
amplification
o Downstream effects are similar on both the left and right side of these images
o It is a cascade of signals
o In the end, there is an activated target protein and different effects
o Everything just described is the pathway on the left
o Pathway on the right is referred to receptor tyrosine kinase
o Difference between the types of receptors, is that there is a phosphorylation of the
receptor itself
o The receptor becomes a recruiting station - attractive to certain kinds of proteins
when it is phosphorylated
o Receptors are phosphorylated and are attractive to certain signalling molecules
o The cascade still occurs on the target proteins which thus causes an effect
o Effects
o Most cells need to have trophic factors, these are signals that tell the cell to stay alive
o When they're not around, the cell can die
o Cell triggers it's suicide pathway and undergo apoptosis when it isn't there
o Cell movement
o Metabolic change - if a certain nutritional element is present, the cell will alter its
metabolic pathway in response to the presence or absence of the nutrient
o Signal transduction- refers to the entirety of the pathway
G Protein Coupled Receptors
o Heterotrimeric G Protein
find more resources at oneclass.com
find more resources at oneclass.com
o Three different parts
o This is always coupled to a G protein coupled receptor
o Coupled to an effector as well
o Represents the left pathway on the previous slide
o These G protein coupled receptors
o Over 1000 of our genes are dedicated to encoding these receptors (about 30,000 genes
in our genomes)
o Responses to adrenaline, many pharmaceuticals, etc.
o They are like fake ligand for transmembrane receptors, as one of them shown on the
right
o Can be called 7 transmembrane receptors due to having 7 domains
o You always have three loops on the outside and three on the inside
o Amino is always on the outside
o Carboxyl is on the inside
o 3 Loops on the outside
o Used to recognize the ligand
o Lots of variety
o 3 loops on the inside
o Less variable
o Involved in activating the g protein
o The G protein is a GTPase
o When 7 transmembrane receptor s activated, causes the GDP to get replaced by GTP
o The G protein coupled receptors is the GEF of the G protein (causes the exchange of
GDP to GTP)
o Alpha subunit is attached by a lipid anchor within the membrane
o Stays close to the membrane
o Gamma/beta subunit are best bros and never separate so they are regarded as one
o G protein will activate an effector, which can be different things, depending on the pathway
o Ex. Adenylyl cyclase - produces a cyclic AMP which was the first second messenger
to be discovered
Receptor Mediated Activation of Effectors by Heterotrimeric G Proteins
o Loops on the inside are going to be able to capture a G protein
o Alpha subunit can bind to the 7 transmembrane domain receptor
o Heterotrimeric G protein is tightly bound together
o The 7 transmembrane domain will change in conformation relative to each other
which will cause an exchange of GDP to GTP on the alpha subunit
o Once GTP replaces GDP it will detach from the receptor
o The Gamma/beta will also detach so the alpha subunit can activate the effector
by itself
o Single ligand can activate multiple G proteins
o Different types of second messengers that exist in cells
o Cyclic AMP
o Calcium
o Phosphoinositide
o Diacylglycerol
o Cyclic GMP
find more resources at oneclass.com
find more resources at oneclass.com
