Signalling Flashcards
What is the importance of signalling in the body?
Human cells are always exposed to changing conditions:
-differences in signal from environment
-temp
-pathogens
-changes in ion conc. in extracellular fluid
-changing levels of nutrients in blood
We need these signals to maintain homeostasis
What is the importance of signalling for tissues and organs?
Tissues and cells need to co-operate to function as organs and tissues.
What type of signals are there?
- Physical (set of a chemical or electrical signal)
- Electrical
- Chemical
How can signals be classified?
Based on chemical structure and by distance over which they act
How can signals be classified by their chemical structure?
- Amino acid derivatives= modified amino acids (eg. adrenaline)
- Peptide hormone= (larger ones=protein hormones) eg. human groth hormone
- Steroid hormones= (derived from cholesterol) eg. testosterone, progesterone
- Eicasonoids= (derived from lipids) eg. prostaglandins
How can signals be classified by the distance over which they act?
- Endocrine= a signal that acts over a long distance (transported via bloodstream)
- Paracrine= releasing a signal to act on nearby cells (signal molecules move by diffusion)
- Juxtacrine= a signal that acts on the neighbouring cell via direct cell-cell contact
- Autocrine= a signal that acts on the same cell that replaces it
What are the basic steps of signalling?
Receptor, transmitting and amplifying signal, response.
What happens when cell signals conflict?
There are a few possibilities:
- cell ignores one and follows other
- signals may work independantly, and cell will produce multiple independant responses
- sometimes, multiple signals will work together to produce an overall cell response.
What type of receptors can act in the receptor stage of signalling?
- Intracellular
- Cell surface receptors
How does the process of reception work with intracellular receptors?
Signals for these need to be able to cross plasma membrane to enter cell and bind to receptor, therefore they are either hydrophobic or are gases so can diffuse through the membrane.
What type of signals use intracellular receptors and give an example?
Lilophilic
eg. lilophilic steroid hormones bind to those receptors and this complex acts as a transcription factor.
This complex binds to DNA and alters gene expression.
What type of cell surface receptors are there and what are some examples of these?
- Ion channel linked (eg. glutamate neurotransmitter)
- G-protein linked (GPCR) (eg. adrenaline, seratonin)
- Enzyme linked (eg. receptor tyrosine kinases (RTK’s), insulin, many growth factors)
How do cell surface receptors work?
Ligand binds to extracellular domain of receptor, causing change in shape of receptor, altering activity of the intracellular part of the receptor, setting the response in motion.
What response is initiated in response to the different types of cell surface receptors?
- Ion channel linked - ion flow into cell changes electrical properties of cell
- G-protein linked- activated g protein activates enzyme that passes on signal into cell
- Enzyme linked- ligand binding > receptor dimerization > autophosphorylation > docking sites > relay proteins recruited > transmit signal further into cell
How many signalling pathways can a receptor activate?
multiple
How many responses can a signalling pathway initiate?
multiple
What are the main methods of transmitting and amplifying signals?
- Kinase/enzyme cascades
- 2nd messengers
How do enzyme cascades work?
- Each step in a cascade is catalytic
- the final enzyme in the cascades alters the function on an effector molecule, which produces the cells response
- this means in addition to passing on the signal, there is amplification of the signal, activation of 1 receptor can therefore affect 1000’s of effector molecules
How do production of 2nd messengers work?
Are small molecules that are produced in large quantities inside the cell after receptor activation, and co-ordinate the cells response.
What are common examples of pathways/molecules that use 2nd messengers?
- cyclic AMP (cAMP)
- Inositol triphosphate (IP3)
- Diaglycerol (DAG)
- Calcium ions
What is an example of a pathway that uses enzyme cascade to transmit a signal?
eg. MAPK pathway
RAS> BRAF> MEK> Response
What are some of the responses to signal pathways?
- changed gene expression
- changed protein activity eg. phosphorylation alters metabolic enzyme activity
- changed protein binding eg. to inhibit/ activate proteins
- changes in protein localisation eg. transcription factors activated by moving from cytosol to nucleus
- alters protein stability
Why is knowledge of signalling pathways important clinically?
Drugs target antibodies and inactivate them, or target small molecule kinases and inhibits.
What is a xynogen?
An inactivated form of a protein
eg. prothrombrin to thrombin
