Cell-cell interactions: TGFbeta and FGF signalling Flashcards
What are the 3 common features in signal transduction pathways?
1) Reception
2) Transduction
3) Response
What happens in the reception stage of a transduction pathway?
Ligand binds to a cell surface receptor and activates it
What can a ligand be?
Extracellular or membrane bound
What happens in the transduction stage of a transduction pathway?
Signal is relayed from the membrane to the nucleus
Via a cascade of secondary messengers
What happens in the response stage of a transduction pathway?
Transcription factor is activated:
- Translocates into the nucleus
- Induces transcription of specific target genes (to activate or repress genes)
What 3 families of molecules fall into the ‘TGF beta superfamily’?
1) BMP-like family
2) GDNF family
3) TGF-beta-like family
What are the members of the BMP-like family of TGF beta molecules?
What are they involved in?
- BMP
- GDF
Involved in development
What are the members of the TGF-beta-like family of TGF beta molecules?
What are they involved in?
- TGF-beta
- Nodal
- Activin
- Veg1
Important role in cancer
What do the members of the TGF beta superfamily share?
What is the exception?
The same mechanism of signal transduction
With the exception of the SMAD proteins that are used - different receptors, different SMAD proteins
Describe the signalling transduction cascade of TGF beta
1) Ligand encounters receptor - first binds to type II receptor
2) Causes the receptor to undergo oligomerisation
- Bings in type I receptor
- Forms dimer with type II receptor
3) Dimer results in the activation of the type II receptor
4) Phosphorylation of type I receptor - triggers overall activation of the receptor
5) Specific SMAD proteins recruited and phosphorylated by the activated receptor
6) SMADs are further activated by SMAD 4 - resulting in an active complex that acts as a transcription factor
7) TF translocates into the nucleus - activating transcription
What activity does the type II receptor have?
What does this promote?
Kinase activity
Promotes the phosphorylation of the type I receptor, triggering the overall activation of the receptor
What is the type II receptor of TGF beta?
Type I receptor?
TGFBR2
TGFBR1
What results in activation of the type II receptor?
Oligomerisation of type I and type II receptors
What are the SMAD proteins that are recruited and phosphorylated by the receptor in the case of TGF-beta ligand?
SMAD 2
SMAD 3
What are the SMAD proteins that are recruited and phosphorylated by the receptor in the case of BMP or GDF ligand?
SMAD 1
SMAD 5
SMAD 8
How is BMP signalling controlled?
Through INHIBITION:
- Regulated extracellularly by antagonists
- Modulate the amount of interaction that BMP and their receptors have
- Different cell fates are dependant on the amount of ANTAGONIST present
What are the antagonists that control BMP signalling?
- Chordin
- Noggin
- Follistatin
- Cerberus
Why is BMP signalling tightly regulated?
How is this easily done?
Want SPECIFIC cells to respond to signal at a SPECIFIC time and a SPECIFIC place
Easily done by having the components of the signalling pathway present but controlling the activity of these proteins through EXTRACELLULAR INHIBITORS
How many families of RTK are there?
What does each family have different?
20 families
Each have individual receptors and ligand partners
What are examples of RTKs?
- Insulin receptor
- NGF receptor
- PDGF receptor
- FGF receptor
- EGP receptor
How do RTKs and their ligands interact?
Some ligands - specific to one receptor, or bind to many
Some receptors - specific to one ligand, or to many
What are 4 common features of all RTKs?
- Mostly monomers (except insulin receptor)
- Extracellular domain varies greatly
- Intracellular domain has kinase activity
- Short, single transmembrane domain
Even though the extracellular domains of RTKs vary greatly, what can be seen?
Recognisable features, like the presence of immunoglobulin domains
How can the kinase domain of an RTK be split?
Into 2 domains
