Signalling Flashcards
Explain why medical students might want to learn about signalling?
Understand how cellular process are regulated.
Understand how embryonic development is coordinated
Explain how faulty signalling causes disease
What is an endocrine signal?
Give an example of one.
Signal that travels long distance (via blood)
Oestrogen
What is a paracrine signal?
Give an example of one.
Signal acts locally I.e on neighbouring cells
Epidermal GF
What is an autocrine signal?
Give an example of one.
Acts on the same cell
Insulin-like growth factor 1
What is an intracrine signal?
Give an example of one.
Signal produced within cell then acts on nuclear or internalised receptor
Fibroblast growth factor 11
What is a juxtacrine signal?
Give an example of one.
Signal on surface of cell directly in contact with receptor on surface of another cell.
Notch
Give an example of a type of signal that is hydrophobic.
Steroid hormone i.e testosterone and oestrogen
Give an example of some signal types which are hydrophilic.
Peptide hormones - insulin, growth hormone
Peptide growth factors
- EPO
Neurotransmitters - ACh
Describe the mechanism of action of a steroid hormone.
Crosses plasma membrane
Binds to internal receptor
Hormone-receptor complex acts as a transcription factor
Directly affects gene transcription
By what mechanism do hydrophilic signals relay their message?
Signal transduction
With regards to hydrophilic signalling, what is a first messenger?
Extracellular ligand
With regards to hydrophilic signalling, what is a secondary messenger?
Intracellular molecule
What are the three main types of receptors that respond to a hydrophilic signal?
Ion-channel linked receptors
Enzyme linked receptors
G-protein linked receptors
What are the 3 stages of signalling?
Reception
Transduction
Response
How do G protein coupled receptors work?
Ligand binds to extracellular domain, causes conformational change in cytoplasmic domain, conformational change allows G protein to bind and be activated (bound to GTP), activated G protein activates downstream enzymes
Name 3 main G protein- alpha subunit effectors.
Adenylyl cyclase - makes cyclic AMP
Phosphlipidase C- makes IP3 + DAG which releases calcium
RhoGEFs
What is the action of cAMP?
Activates protein kinase A
Activated PKA phosphorylates many downstream target proteins
What do second messengers do?
Activate/inhibit many different target proteins
Where are alpha-1, alpha-2, beta-1 and beta-2 adrenergic receptors located?
Alpha-1&2 - vascular smooth muscle
Beta-1 - cardiac muscle
Beta-2 - airway smooth muscle
Give examples of RTKs.
EGF, FGF, insulin
How to receptor tyrosine kinases work?
Ligand binds to extracellular receptor
Receptor dimerises
Cytoplasmic domains have tyrosine kinase activity
Allows cross phosphorylation
Phosphorylated receptor acts as docking site for intracellular signalling proteins
Downstream signalling activated
Give an example of a drug which targets a receptor tyrosine kinase.
Drug: Herceptin
Target: HER2 (human EGFR2)
Drug type: antibody
Treats: HER2 positive-breast cancer
How does acetyl choline work at the NMJ?
ACh released from motor neurone
ACh binds to receptor on muscle cell and channel opens
Na+ ions enter, cause an action potential
Action potential causes muscle contraction
Acetylcholinesterase enzyme switch off signal
How to drugs for myasthenia gravis improve muscle strength?
AChE inhibitors inhibit acetylcholineesterase, enhancing neuromuscular transmission
