Superfamily 3 Flashcards
(48 cards)
What is the name for SF 3 receptors?
Enzyme linked receptors
What is the structure of an SF 3 receptor?
An amine group? (NH2)
Agonist binding site
Catalytic domain
COOG group?
N and C terminals are connected by one transmembrane alpha helix
What receptors are linked to tyrosine kinase?
Insulin receptor
Insulin-like growth factor receptor
Epidermal growth factor receptor
Cytokine receptors
What receptors are linked to guanylate cyclase?
Atrial natriuretic peptide (ANP) receptor
Guanylin receptor family
Photoreceptor dark cycle
What bonds holds the two alpha units in an insulin receptor?
A sulphur bond
1 holds the entire molecule together
2 hold the individual elements together
Give an interesting fact about tyrosine kinase
More than 90 tyrosine kinases have been identified but only 2/3 are receptor linked
What happens when an agonist binds to a tyrosine kinases linked receptor?
Altered conformation results in (augmented) receptor dimerisation
Is SF 3 are large family?
No it is relatively small and most of its receptors are linked to tyrosine kinase
What is different about the insulin receptor?
It is a loose dimer at rest
What are the steps of activation of tyrosine kinase receptors?
Rest
Conformational change (dimer formation)
Tyrosine autophosphorylation
Binding and phosphorylation of SH2 domain protein
When will SH2 proteins bind to the tyrosine kinase protein?
Only when the tyrosine molecules have been phosphorylated
What happens when the SH2 domain protein binds to the phosphorylated tyrosine?
The SH2 proteins become phosphorylated themselves and change shape - altering their own activity pathways
Explain how each tyrosine molecule becomes activated
If a tyrosine molecule is phosphorylated by a neighbouring dimer then there is potential for the 3 tyrosine molecules of each dimer to be activated
This can enhance activity by 200 fold if all three are activated
What about additional tyrosine sites within the receptors?
If these tyrosine sites are also activated they can then act as anchor points for the SH2 domains
How can tyrosine kinase receptors bind multiple SH2 domains at once?
Due to the multiple tyrosine sites
Explain the name SH2 domain
It appeared similar to the src oncogene production
Homologous to Src = SH2
How large is the SH2?
It is only 100 amino acids long, it is a smaller part of a larger protein
Why can SH2 be thought of as a jig saw piece?
The SH2 domain is meant to recognise phosphorylated elements of other proteins and bind/ attach to them
The way a jig saw piece would have to match another piece before connecting to it
If the SH2 domain cannot bind directly to Tyrosine kinase what must it use?
If the SH2 is binding indirectly then it will be done via docking proteins
These must also be phosphorylated before SH2 can bind to them
What is the purpose of the SH2 domain?
They can act as adaptors - meaning they can act as bridge connecting to the tyrosine kinase to other molecules
More often though they contain enzymes and transcription factors
Give examples of proteins that contain a SH2 domain
RAS (small G protein) that activates mitogen activated protein kinases resulting in a signalling cascade
Phospholipase C gamma
Glucose transport proteins responsible for glucose uptake across cell membranes
Transcription factors that once activated by tyrosine kinase will translocate to the nucleus
What is the thinking behind internalisation of activated receptor tyrosine kinases?
Initially thought to be involved in receptor desentisation, degradation and eventually recycling back to the cell surface
Now thought to also play a role in additional signalling to sub cellular targets such as nucleoplasm and mitochondria
What are the thoughts behind activated tyrosine kinase works internally?
First assumed that the entire receptor protein would be trafficked in this way however it is more likely that only part of the receptor is trafficked this way
What two things are responsible for moving part of the tyrosine kinase to work internally?
Secretases
Caspases
