Cell Signalling Flashcards
What are the 8 general principles of cell signalling?
1 - Cell synthesizes signalling molecule
2 - This is released
3 - Transported to the target cell
4 - Activation of receptor
5 - Signal transduction pathway
6 - Short-term effect (function, metabolism, movement) or long-term effect (gene expression)
7+8 - Termination by inhibition or removal of signalling molecule
Describe the general pathway by which a signal produces a response in a cell after activating the receptor
- Receptor activates the relay molecule
- Transducer changes the form of the signal and produces second messengers which amplify the signal
- Range of proteins activated which can bring signals from multiple pathways together (integrator)
- Distributor can then enact changes on cell function
What 4 things make an effective signal?
- Specificity - defined cellular outcome
- Small - rapidly diffuse across membranes
- Made, mobilised & altered quickly
- Amplification
When does maximal physiological response occur in response to an extracellular signal?
When only a fraction of receptors are occupied by a ligand
What gives more opportunity for amplification?
- Steps in the signal transduction process
- Also makes for a more dynamic, easily regulated system
Name 5 mechanisms for the termination of cell signalling
- Receptor sequestration
- Receptor down-regulation
- Receptor inactivation
- Inactivation of signalling protein
- Production of inhibitory protein
What is juxtacrine signalling?
- Does not involve chemical messenger release
- 2 neighbouring cells communicate via physical connections
- Important for embryonic development
Describe notch signalling
- Notch receptor on one cell targets receptors delta and serrate
- Causes proteolysis of intracellular region of notch
- Alters gene expression
What is autocrine signalling?
- When a cell releasing a messenger also recieves said messenger
- e.g Interleukin, Wnt, cancer cells
What is paracrine signalling?
- When a chemical messenger diffuses across the extracellular matrix and activates neighbouring cells
- Found in fibroblasts
What is endocrine signalling?
When secreting cell releases chemical into the blood stream which goes on to target distant cells
What are the 3 classes of hormones?
- Peptide/protein
- Steroids (neutral lipids derived from cholesterol)
- Amines derived from tyrosine
How are peptide proteins produced?
Produced by transcription/translation as prehormones which are then cleaved to form prohormones which are cleaved again to produce active hormones
Describe steroid hormones and give examples
- Derived from 80% blood LDL cholesterol and 20% acetylcholine
- e.g cortisol, testosterone, estradiol
Describe amine hormones
- Derived from tyrosine
- Each has their own synthetic pathway and storage site
What are the 2 types of cell membrane receptors?
single membrane-spanning and multi membrane-spanning
What is the major function of G coupled receptors?
The regulation of enzymes and proteins, allowing the cell to quickly respond to its environment
What is the structure of tyrosine kinase receptors (RTKs)?
- Single-pass with an intracellular tyrosine kinase
- Usually dimerise to function
What do RTKs usually affect?
Predominantly bind to growth factors to influence transcription and cell proliferation/differentiation
How do RTKs function?
Initiate phosphorylation via the tyrosine kinase domain for the recruitment of transducer proteins which then couple with amplifiers
What is the structure of serine/threonine kinase linked receptors?
- single pass
- serine/threonine intracellular domain
How do serine/threonine kinase linked receptors function?
- Serine/threonine acts as both a transducer and an amplifier
- Recruits protein SMADS which then interacts with the nucleus in order to regulate gene expression
Where can ion channels be found acting as receptors?
In neurons where they act as both transducers and amplifiers which can go on to have an effect on gene transcription or function
What is the structure of G coupled receptors (GPCRs)?
- 7 transmembrane regions with 3 extracellular and cytosolic loops
- G protein bind to C3 and C4
- Ligand binds to the extracellular side
Describe the activation of a GPCR
- Ligand bonds to the receptor causing G protein to be recruited
- G protein allows GTP to bind to G alpha, causing the G protein to activate and for the alpha subunit to detatch from the beta and theta subunit
- Subunit activates effector protein to transduce the message and bring about cellular change
What are the 4 second messengers used by GPCRs?
- Cyclic AMP
- Cyclic GMP
- Diacylglycerol
- Inositol triphosphate
How does the GPCR pathway activate protein kinase A (PKA)?
- Activated G protein goes on to hydrolyse ATP to cyclic AMP
- This then binds to PKA via a regulatory subunit which releases the catalytic subunit and activates the PKA
What are the 4 ways in which a GPCR signal can be downregulated?
- Loss of receptor affinity for the ligand
- Inhibition of the receptor
- Downregulation of the second messenger
- Ubiquitination
Describe how the GPCR may lose affinity for a ligand
Due to innate GTPase activity in the G alpha subunit, GTP is hydrolysed back to GDP causing the protein to become inactivated
Describe the process feedback repression in PKA
PKA phosphorylates the receptor intracellular region by the recruitment of a large protein complex, causing inactivation of the receptor
Describe how the downregulation of PKA can occur in the case of a second messenger
- At resting state, PKA is bound to the membrane via mAKAP and PDE which degrades cyclic AMP
- Increasing cAMP activity leads to PKA activation, which goes on to phosphorylate PDE which increases its activity
- cAMP is quickly degraded and levels return to normal
What is ubiquitination?
Where the addition of the small protein ubiquitin targets a protein to be broken up, or for the degradation of a receptor
