Monday, 7 June y
BIOC 2003
Signal Transduction Processes
General Signal Transduction
The hormone is released. Hormone is the primary messenger. Can act in on targets
nearby to its release or all over the body.
Hormone then binds to a receptor expressed by the cell to cause a conformational
change in its cytosolic region to alter its function.
The concentration of the second messenger (small sugar or ion) then increases through
enzymatic action.
The effectors (proteins that carry out the task) are then stimulated or inhibited by the
second messenger. Effectors can be pumps, enzymes or gene transcription factors for
example.
The signal is shut down- it either becomes desensitised to the stimulus or the stimulus is
removed. Often an enzyme that breaks down the secondary messenger or desensitisa-
tion e.g. in diabetes type II and insulin
Specificity
• hormone is released into a specific area
• the binding is specific- specific receptors for specific hormones
• intracellular domain can have different effects e.g. the ligand binding domain of two
different receptors can bind the same hormone but have different effects due to the in-
tracellular domain activating different second messengers
• secondary messengers have specific effects that depend on both the hormone bind-
ing and the type of receptor
• different cells express different isoforms of the effector- genome has lots of exons but
only a certain amount will be expressed determining the receptor
Sensitivity
• small concentration of hormone can cause a large effect e.g. insulin
• hormone receptors have a high affinity for their hormone
• many second messengers are activated by one receptor (amplification)
• some effectors can be stimulated and some inhibited (can tune the pathway)
Integration
1
, Monday, 7 June y
• hormones can work together to monitor the outcome of a cell
• cells express multiple hormone receptors on their surface
• the different receptors can bind to the different (or same) hormones at the same time
so the intracellular domains change at the same time which can lead to predictable or
unpredictable results
• different receptors can work together e.g. one can activate a second messenger and
the other can inhibit it when activated by the same hormone
• different signalling pathways can alter the same effectors to give fine-tuning
Allosteric effects (conformational changes)
Examples of allosteric effects:
• Hormones binding to receptors- conformational change in the cytosolic domain
• GPCRs cause a conformational change in G protein- alpha subunit dissociates from
beta/gamma subunits
• Calcium exposes hydrophobic areas that allow the calmodulin to interact with other
proteins
• cAMP causes the regulatory subunits of the PKAR to dissociate, activating the cat-
alytic subunits
Phosphorylation
• Catalysed by protein kinases and hydrolysis of ATP, to remove the phosphate an en-
zyme -phosphatase- is used
• Negative charges of phosphorylation can disrupt electrostatic interactions
• The phosphoryl group can form several H bonds
• Can be inhibitory or stimulatory- some proteins have activating and inhibiting phos-
phorylation sites
• Two main classes of protein kinases; serine/threonine kinases and tyrosine kinases
• Each kinase phosphorylates residues in a particular consensus sequence that can be
found on its target proteins- kinases are specific
• Each kinase can phosphorylate multiple target proteins, so they represent points in
the signalling pathway where the signal can be amplified
Protein Domains
• Protein domains are folds of peptides that are seen fairly commonly
• they have a high affinity for certain types of sequences
• Different protein domains:
2
BIOC 2003
Signal Transduction Processes
General Signal Transduction
The hormone is released. Hormone is the primary messenger. Can act in on targets
nearby to its release or all over the body.
Hormone then binds to a receptor expressed by the cell to cause a conformational
change in its cytosolic region to alter its function.
The concentration of the second messenger (small sugar or ion) then increases through
enzymatic action.
The effectors (proteins that carry out the task) are then stimulated or inhibited by the
second messenger. Effectors can be pumps, enzymes or gene transcription factors for
example.
The signal is shut down- it either becomes desensitised to the stimulus or the stimulus is
removed. Often an enzyme that breaks down the secondary messenger or desensitisa-
tion e.g. in diabetes type II and insulin
Specificity
• hormone is released into a specific area
• the binding is specific- specific receptors for specific hormones
• intracellular domain can have different effects e.g. the ligand binding domain of two
different receptors can bind the same hormone but have different effects due to the in-
tracellular domain activating different second messengers
• secondary messengers have specific effects that depend on both the hormone bind-
ing and the type of receptor
• different cells express different isoforms of the effector- genome has lots of exons but
only a certain amount will be expressed determining the receptor
Sensitivity
• small concentration of hormone can cause a large effect e.g. insulin
• hormone receptors have a high affinity for their hormone
• many second messengers are activated by one receptor (amplification)
• some effectors can be stimulated and some inhibited (can tune the pathway)
Integration
1
, Monday, 7 June y
• hormones can work together to monitor the outcome of a cell
• cells express multiple hormone receptors on their surface
• the different receptors can bind to the different (or same) hormones at the same time
so the intracellular domains change at the same time which can lead to predictable or
unpredictable results
• different receptors can work together e.g. one can activate a second messenger and
the other can inhibit it when activated by the same hormone
• different signalling pathways can alter the same effectors to give fine-tuning
Allosteric effects (conformational changes)
Examples of allosteric effects:
• Hormones binding to receptors- conformational change in the cytosolic domain
• GPCRs cause a conformational change in G protein- alpha subunit dissociates from
beta/gamma subunits
• Calcium exposes hydrophobic areas that allow the calmodulin to interact with other
proteins
• cAMP causes the regulatory subunits of the PKAR to dissociate, activating the cat-
alytic subunits
Phosphorylation
• Catalysed by protein kinases and hydrolysis of ATP, to remove the phosphate an en-
zyme -phosphatase- is used
• Negative charges of phosphorylation can disrupt electrostatic interactions
• The phosphoryl group can form several H bonds
• Can be inhibitory or stimulatory- some proteins have activating and inhibiting phos-
phorylation sites
• Two main classes of protein kinases; serine/threonine kinases and tyrosine kinases
• Each kinase phosphorylates residues in a particular consensus sequence that can be
found on its target proteins- kinases are specific
• Each kinase can phosphorylate multiple target proteins, so they represent points in
the signalling pathway where the signal can be amplified
Protein Domains
• Protein domains are folds of peptides that are seen fairly commonly
• they have a high affinity for certain types of sequences
• Different protein domains:
2
