Lecture 5 Flashcards
What is the signal transduction mechanism?
- Signal - Chemical or physical (extracellular activator of the pathway)
- Reception - Detection of the signal by a receptor protein
- Transduction - Proteins that help transduce the signal from one place to another
- Amplification - Secondary messengers and signal cascades
- Response - Change in cellular processes (e.g gene expression, enzyme activity, cell structure)
What can alter the activity of the proteins in a signalling pathway?
- The level of the protein (abundance) [A slow process]
- A change in activity of a fixed amount of protein by either conformational changes or by covalent modification (phosphorylation) [A fast process]
What are signalling proteins acting as?
Molecular switches
Where can the receptors be found?
They can be located either on the cell surface or inside of the cell itself
How do the signalling molecules reach the intracellular receptors?
They are small hydrophobic molecules that can cross the cell membrane e.g steroids
What is different about the signalling molecules that bind to the cell surface instead of intracellularly?
They are hydrophilic molecules which cannot cross the cells membrane and therefore can only bind to cell-surface receptors e.g neurotransmitters
Different responses from cells need a different combination of signals to produce that result. Give examples of the outcomes of different cellular signalling pathways
- Survival of the cell
- Cell division
- Cell differentiation
- Cell death
What are the 4 primary areas of hormone action?
- Reproduction
- Growth and development
- Maintenance of internal environment (homeostasis)
- Energy production, utilisation and storage
What are the functions of these hormones and where are they produced?
Insulin, Glucagon, Oxytocin and Vasopressin
Insulin (pancreas) - Controls blood sugar levels and storage of glycogen
Glucagon (pancreas) - Stimulates conversion of glycogen into glucose which raises blood sugar level
Oxytocin (pituitary gland) - Stimulates contraction of the uterine muscles and the secretion of milk by the mammary glands
Vasopressin (pituitary gland) - Controls water excretion by the kidneys and stimulates the contraction of blood vessels
What is a common signalling pathway showing the activation and inactivation of the proteins (molecular switches)?
The signal reaches the protein —> a kinase enzyme phosphorylates the protein and therefore the protein is switched on —> a phosphatase enzyme can dephosphorylate the ‘on switch’ and this would turn the switch back off
What is a kinase?
It is an enzyme that transfers phosphate groups to a protein or other target
How does a tyrosine kinase work?
The tyrosine residue reacts with ATP causing the loss of a phosphate group and the production of ADP, the phosphate group is then bonded onto the hydroxyl group of a protein. It is now phosphorylated
How are tyrosine kinases activated by insulin binding?
- Insulin binds to a receptor that is wholly extracellular
- The binding of the insulin causes the intracellular kinase domain to undergo autophosphorylation activating it
What proteins become deregulated in order to cause cancer?
The MAPKs (mitogen-activated protein kinases)
What do normally activated MAPKs do in the body?
They phosphorylated specific transcription factors which are then translocated to the nucleus, these activated transcription factors and kinases induce cellular responses e.g growth and differentiation (this is how the tumours are signalled to grow)
What are the heterotrimeric G proteins?
They are proteins that are members of the superfamily of regulatory GTPases (G proteins) their job is to hydrolyse GTP into GDP and Pi
Give an example of a signalling pathway including a G protein
- Signal molecule binds to a G protein-linked receptor, which activates the G protein
- The G protein then binds to Adenylyl cyclase (an amplifier enzyme) activating it
- Adenylyl cyclase then converts ATP into cAMP (cyclic AMP)
- cAMP then activates protein kinase A
- Protein kinase A phosphorylates other proteins, leading ultimately to a cellular response
What does the signalling cascade do?
The signalling cascade amplifies the signal of the bound signal molecule that started the whole process
What are the components that make up the plasma membrane?
Lipids - Phospholipids and sterols
Proteins - Integral, peripheral, channel, globular and alpha helix
Carbohydrates - Glycolipids and Glycoproteins
What are the transport mechanisms to get products across the cell membrane?
Passive transport - simple diffusion, [channel-medicated diffusion or carrier medicated diffusion - facilitated diffusion] With the concentration gradient
Active transport - Against the concentration gradient (needs ATP)
What are some of the different methods of active transport?
- Coupled transporter
- ATP-driven pump
- Light-driven pump
What does the Na+/K+ pump work?
The pump hydrolyses ATP to ADP which leads to the transportation of 3Na+ ions out of the cell and 2 K+ ions into the cell per cycle
This all happens through conformational changes in the pump and its affinity for certain molecules in certain states
