Cell Signalling Flashcards
What is a ligand?
Any molecule or ion that binds to protein surface by non covalent bonds e.g. hormone or neurotransmitter.
What is a ligand gated ion channel?
A membrane-bound receptor protein that responds to ligand binding by opening an ion channel and allowing ions to flow into the cell.
Describe how ligand-gated ion channels work.
- Ligand binds to receptor on or in target cell
- This causes a conformational change in the receptor (protein) i.e. it changes shape, such that it forms and open channel through the plasma membrane through which some ions can flow.
Give an example of a ligand-gated ion channel.
Nicotinic Acetylcholine receptor
When ACh binds this alters the conformation of the receptor which allows Na+ to flow into the cell and depolarise the postsynaptic cell.
What is the difference between an Antagonist and an Agonist?
- An antagonist is a molecule that competes with a ligand for binding to its receptor, but does not activate signalling normally associated with the ligand so has no effect.
- An agonist is a chemical messenger that binds to a receptor and triggers the cell’s response - has the same effect as the ligand.
Both have active sites of similar shape to the ligand, but the antagonist is not close enough to produce an effect so simply prevents the ligand from binding.
What is down regulation?
A decrease in the total number or target-cell receptors for a given messenger. This can occur in response to a high concentration of messenger e.g. high levels of insulin result in a down regulation of insulin receptors making the body less sensitive to insulin.
What is up regulation?
An increase in the total number of receptors for a given messenger. This many occur in chronic low concentrations of the messenger.
What are protein kinases?
What are receptor tyrosine kinases?
- Enzymes that phosphorylate other proteins by transfer of a phosphate group to them from ATP.
- The majority of protein kinases specifically phosphorylate the portions of proteins that contain the amino acid tyrosine thus are called receptor tyrosine kinases.
Describe how receptor tyrosine kinases work.
- The binding of a ligand to the receptor changes the conformation of the receptor and causes neighbouring RTKs to associate with each other forming a cross-linked dimer.
- This activates the tyrosine kinase activity. Each RTK in the dimer phosphorylates the tyrosine on the other RTK in a process called cross-phosphorylation.
- The newly created phosphotyrosines on the cytoplasmic portion of the receptor then serve as docking sites for cytoplasmic proteins.
- The bound docking proteins then bind and activate other proteins which in turn activate one or more signalling pathways within the cell.
Describe how ligands work through G-protein coupled receptors.
- The binding of a first messenger to the receptor changes the conformation of the receptor.
- This increases the affinity of the alpha subunit of the G protein for GTP.
- When bound to GTP, the alpha subunit dissociates from the remaining two subunits (beta and gamma), activating it.
- The dissociated alpha subunit can now move through the plasma membrane and bind to another protein (ion channel or enzyme).
- Once it has activated its protein, the GTP is hydrolysed to GDP and Pi, inactivating the alpha subunit which re-associates with beta and gamma.
Essential, a G-protein serves as a switch to couple a receptor to an ion channel or to an enzyme in the plasma membrane.
Give and example of a G-protein coupled receptor.
Adrenaline receptor:
- Adrenaline binds and changes conformation of receptor.
- Alpha subunit dissociates and activates adenylate cyclase (AC)
- AC catalyses the conversion of ATP into cAMP (cyclic adenosine monophosphate) in the cytoplasm
- cAMP binds and activates Protein Kinase A
- Protein Kinase A phosphorylates a protein to activate (or deactivate) it.
e.g. in the Liver adrenaline acts via cAMP to stimulate both glycogeneolysis and gluconeogenesis.
Explain how caffeine and theophylline, the active ingredients of coffee and tea, work.
The action of cAMP terminates when it is broken down to noncyclic AMP, which is catalysed by the enzyme phosphodiesterase. Caffeine and theophylline work partly by inhibiting phosphodiesterase activity thus prolonging the actions of cAMP in the cell.
Explain how caffeine and theophylline, the active ingredients of coffee and tea, work.
The action of cAMP terminates when it is broken down to noncyclic AMP, which is catalysed by the enzyme phosphodiesterase. Caffeine and theophylline work partly by inhibiting phosphodiesterase activity thus prolonging the actions of cAMP in the cell.
Explain how one molecule of the hormone adrenaline can cause the liver to generate and release 10^8 glucose molecules.
Amplification Cascade
- While it is active, a single enzyme molecule is capable of transforming into product many substrate molecules. Thus one active molecule of adenylate cyclase could catalyse the generation of 100 cAMP molecules. At each of the two subsequent enzyme-activation steps another 100-fold amplification occurs.
Describe the action of G-protein coupled receptors in activating a membrane bound phospholipase (phospholipase C)
- First messenger binds the receptor changing its conformation.
- The alpha subunit dissociates and activates a membrane bound phospholipase (phospholipase C) e.g. gut hormone CCK.
- Activated PLC causes the hydrolysis of PIP2 (a membrane phospholipid) to produce 2 major products:
- Diacylglycerol (DAG)
- Inositol trisphosphate (IP3) - DAG activates protein kinase C, which then phosphorylates a large number of other proteins leading to the cells response
- IP3 binds to receptors on the endoplasmic reticulum. These are ligand-gated calcium channels which open when IP3 is bound.
- Calcium diffuses down a concentration gradient from the ER into the cytosol.
- Released calcium bind to a protein called Calmodulin changing its conformation
- Ca2+ - calmodulin complex activates a number of enzymes including protein kinases
So DAG and Ca2+ asti together to activate protein kinase C.
