Week 4 - Cell Signalling Flashcards
What is Herceptin’s target
HER2
What is salbutamol’s target
Cell surface receptor (beta 2 receptor)
What is imatinib’s target (used to treat CML)
Intracellular protein tyrosine kinase (Bcr-Abl)
What is bevacizumab’s target
VEGF which is the signal for angiogenesis
In which 2 ways can biochemical signals be classified
Chemical structure and range of action (distance)
Why is cell signalling important?
(3)
To coordinate development
To maintain normal physiological function
If signalling is abnormal, it can cause disease
3 types of signalling molecules
Amino acid derivatives
-Adrenaline (modified aa)
- Oxytocin (peptide hormone)
- Insulin (insulin, growth hormone)
Steroid hormones (derived from cholesterol)
- Testosterone
Eicosanoids (derived from lipids)
e.g prostaglandin
What is the name for long distance chemical signalling
Endocrine - via blood
What is the name for chemical signalling between nearby cells
Paracrine
What is the name for chemical signalling via cell:cell contact
Juxtacrine
What is the name for chemical signalling from the same cell
Autocrine
What are the 3 stages of signal transduction
Detection
Transduction
Response
How do hydrophobic signal molecules reach their receptor
Through the membrane as they are hydrophobic
Examples of hydrophobic signalling molecules
Steroid hormones - oestrogen/testosterone
Nitric acid (g)
What is the steroid hormone’s mechanism of action
Steroid hormone diffuses through the membrane and binds directly to the intracellular receptor proteins
The hormone-receptor complex acts as a transcription factor which binds to DNA and alters gene expression
Example of a hydrophobic signalling molecule
Steroid hormone
Example of a hydrophilic signalling molecule
Insulin/adrenaline
What must hydrophilic signalling molecules use to cause a response
They must use a cell surface receptor protein
What are the 3 main types of cell surface receptors and give an example
Ion-channel-linked
(glutamate neurotransmitter)
G-protein-linked (GPCR)
(adrenaline, serotonin)
Enzyme-linked
(RTK, growth factors, insulin)
Describe the mechanism of an ion-channel-linked receptor
Signal molecule binds to receptor on receptor. Ion flow into cell changes electrical properties of the cell
Describe the mechanism of a G-protein-linked/coupled (GPCR)
Signal molecule binds to activated G protein which then activates enzyme that passes on signal into cell
Describe the mechanism of the enzyme-linked receptor
Signal molecule binds to receptor, bringing the receptor together (dimerisation) which then goes on to activate an intracellular enzyme
Which enzyme phosphorylates molecules
Kinase
Which enzyme dephosphorylates molecules
Dephosphatase
Outline the mechanism of the enzyme-linked receptor RTK (receptor tyrosine kinase)
Signalling molecule binds to receptor, receptor is pulled closer together, dimerisation occurs. Tyrosine is phosphorylated by kinase, which act as a docking station for intracellular proteins
Two methods of transduction
Enzyme cascades
Second messengers
When are MAPK cascades often activated
In response to RTK activation by growth factors (receptor tyrosine kinases) e.g EGF
What type of cascade is an MAPK
An enzyme cascade
What is often activated in response to growth factor RTK activation e.g by EGF
MAPK cascades
What happens before an MAPK cascade after phosphorylation of tyrosine occurs
Relay proteins such as Grb/Sos activate the proto oncogene RAS
MAP kinase cascade is activated
Signal is amplified
What is a second messenger
Small molecule produced in large amounts inside the cell after receptor activation
Give an example of a second messenger
cAMP
How do second messengers result in cellular response
Signal molecule binds, G protein is activated and activates the
Enzyme. Enzyme converts ATP into lots of cAMP. cAMP binds to
Molecule callsed protein kinase A and activates it. The kinase
Can then be used to phosphorylate lots of different target proteins.
Name 3 other second messengers other than cAMP
DAG which activates PKA
IP3 which causes Ca2+ release
Ca2+ which activates Ca-dependent enzymes including CaMKs
What is the typical pairings of GPCRs/RTKs and second messengers/MAPK
GPCRs usually activate second messengers
RTKs usually activate MAPK cascades
Name 4 different responses possible as a result of signal molecule reception and transduction
Gene expression
Protein activity
Protein binding
Protein localisation
What do drugs ending in AB do
Use antibodies to inactivate them and block the signalling pathway
What do drugs ending in IB do
They use small molecule kinase inhibitors to block the signal pathway
Which pathways are usually overactive in cancer
Growth factor
Receptor Tyrosine Kinase
What does herceptin target
It targets the factors that produce the human epidermal growth receptor
What does Bevacizumab target
VEGF (vascular endothelial GF) which prevents angiogenesis
What does Gefitinib target
Iti inhibits EGFR receptor (lung cancer)
When G protein is active, which nucleotide is bound to alpha subunit
GTP
When G protein is inactive, which nucleotide is bound to alpha subunit
GDP
How is G protein deactivated
GAP protein hydrolyses G protein into GDP
Effector proteins produced as a result of activated G protein can do what
Can activate or inhibit targets, directly or indirectly
During glucose release caused by adrenaline, what are the two pathways that can result from phosphorylated kinase activator
Activation of kinase which phosphorylase glycogen into glucose
OR
Activation of glycogen synthase which phosphorylase glycogen synthase which de phosphorylases glucose into glycogen
What happens when adrenaline no longer binds to receptor, this triggers what?
This causes the G protein subunit to no longer be activated. Phosphodiesterase removes the residual cAMP
Can signalling molecules activate singular pathways or multiple
They can activate multiple!
How is specificity in signalling achieved?
The factors that contribute to variation are:
The type of receptor
The G protein involved
The effector enzyme
The second messenger produced
Why shouldn’t you give a patient with heart problems beta blockers if they also have asthma?
you don’t want to give a patient with heart condition AND asthma beta blockers because it will have an antagonistic effect on bronchodilation!
