9. Receptors and signal transduction Flashcards
What’s going on here?
There is a signal attached to the end of the polypeptide chain while its being elongated by the ribosome/tRNA. They both bind to a receptor protein in the endoplasmic reticulum. The signal sequence is removed from the polypeptide chain. Elongation continues until termination and then is retained inside the ER.
What are receptors? Where are they found?
Receptors are a way to transfer complex information across a cell. They are found embedded in the cell membranes. Usually don’t actually transport molecules across cell membrane, but ligands bind to them and then they transmit that information to the cell interior.
What’s happening here?
There’s an external stressor (ex: drought). A drought-sensitive transcription factor activates the transcription of a regulatory protein.
The regulatory protein will bind to the stress response element stimulates transcription of genes A, B and C. Genes A, B and C will produce different proteins participating in the stress response.
What’s the difference between chemical signalling and local signaling?
Chemical signalling involves the release of hormones (ex: adrenaline, insulin)
Local signalling is the communication across a cell through receptor-ligand binding.
What is happening here?
A signal (ligand) binding to a receptor which then causes a change in the structure of the receptor, exposing its active site. A signal transduction molecule can then become activated and eventually bring about cellular change.
How does caffeine work?
Caffeine binds to the same receptor as adenosine, so it can not make you sleeper anymore.
Whats this?
Receptor and ligand (signal). Together they are a complex.
Can signals pass the cell membrane? If they do where do they bind? Whats an example?
Non polar (non-charged) signals can cross membrane and bind to a receptor in the cells cytoplasm. Cortisol is an example of a non polar signal
Whats phosphorylation?
Adding a phosphate group to receptor to activate it.
What is a possible result of receptor-ligand binding?
Signal transduction and physiological response in cell
What’s kinase?
A type of enzyme that adds phosphates to other molecules.
What is a substrate?
A molecule that is acted upon by an enzyme.
When the concentration of ligand increases, what happens to the concentration of complexes?
It increases until all the receptors are saturated and no more complexes can be made.
What is shown here?
x-axis is ligand concentration
y-axis is fraction of complexes/receptors
Draw down from 50% of the max value (C/R = 1) to find the Kd for ligand binding.
Theres a non linear relationship between physiological response and ligand concentration.
What are the variables here?
What does it mean when we assume excess ligand vs not excess ligand?
Must use different formulas
Excess ligand: The amount of free ligand basically equals the amount of total ligand.
(use C = RT·Lo/(Kd+Lo)
Not excess ligand: The amount of ligand that has bound is not negligible relative to total ligand.
(use ueq)
Number of complexes = (total receptor · ligand) / (total receptors + ligand)
What does this equation mean?
Ligand concentration is measure in mol/L
Complex and receptor concentrations are measured in #/cell
Lo = L + C
-> must convert C into mol/L
(#/cell)· (#cell/L) · (1mol/Navo) = mol/L
We know that the initial ligand concentration is equal to the free ligand + the complexes (binded ligands)
Explain the different components in this diagram.
Competitive binding assay
IP = agonist of EP receptor (agonists substitute for ligands) (drugs to fix low ligand concentration)
AP = antagonist of EP receptor (antagonists bind to EP receptor and block its function) (B-blocker)
EP = natural hormone that binds to EP receptor
IP, AP and EP all bind to EP receptor. IP binds at a higher rate because its dissociation constant is lower
What is shown here? What response will we focus on?
Different receptors communicate different things. We will focus on G protein-coupled receptors.
What’s the difference between direct and indirect signal transduction?
In direct signal transduction, a signal binds to a receptor and activates its cytoplasm side, which directly activates an effector protein that initiates the cell’s response. (everything happens at the cell membrane)
In indirect transduction, a signal binds to a receptor protein and the effector protein triggers a second messenger is formed that amplifies the signal. (happens inside the cell)
What’s a common second messenger involved in indirect transduction?
The second messenger is cyclic AMP (adenosine monophosphate)
What are some standard second messengers?
(first messenger = ligand)
What’s happening here?
Signal (ligand) is binding to the G-protein linked receptor, which then activates the inactive G protein.
GDP becomes GTP (meaning G protein is active)
Part of the activated G protein activates an effector protein that amplifies the signal
What’s happening here?
Both activation and inhibition is possible. This shows epinephrine binding and the antagonist adenosine
( ex: For the same physiological effect: epinephrine activates glucose metabolism in skeletal muscles but causes muscle relaxation in smooth muscle cells )
What effect does epinephrine signal have?
- increase heart rate
- constrict blood vessels in intestine
- relaxing vessels in muscles
Caused by inhibiting and activating G proteins in diff tissues
The picture shows that the one molecule of epinephrine will cause many cAMP molecules and there are a cascade of reactions. Epinephrine in liver inhibits glucose storage, and enables glucose breakdown
How is signal amplified?
Through cascade of reactions.
For 1 ligand there are 20-100 cAMP
More enzyme steps = more amplification
Describe this Protein Kinase cascade
series of proteins sequentially activated by phosphorylation, which amplifies the signal
(Kinase refers to a phosphorylation step)
What are three ways of regulating the signal?
- Protein phosphatase (removes phosphate)
- GTPase (removes GTP from active G protein)
- Phosphodiesterase (turns cAMP to AMP)
Explain what’s happening here.
