CellSig12 - 19 Flashcards
How is TGF-b involved in cancer?
Hypomorphic mutations frequently found in patients suffering - likely a tumour suppressor under normal conditions
What are microsatellites?
Repeated sequences that cause problems during DNA replication - can increase or decrease in length
Why are amorphic TGF-b mutations less dangerous?
Cancers use TGF-b later for angiogenesis and mesenchymal invasion transition
What is TGF-b precursor cleaved into?
TGF-b dimers (C-terminal), LAP (N-terminal)
What is LAP?
Latency associated protein
What is LAP tethered to?
EC matrix by LTBP
What is LTBP?
Latent TGF-b binding protein
What releases the LAP/TGF-b dimer complex from the EC matrix?
Proteases, and binding of thrombospondin to LAP
Characterise the TGF-b receptor structure
Enzyme linked - serine/threonine kinase domain
Outline the function of TGF-b receptors
Type II homodimer binds TGF-b dimer, recruiting and phosphorylating type I homodimer
How is lefty involved in TGF-b pathways?
Competes with TGF-b, but lack the alpha helix loop required for receptor dimerisation, so don’t activate the pathway
How is bambi involved in TGF-b pathways?
Decoy receptors, resemble type I receptor, but lacks IC domain, forming inactive complex upon dimerisation with type II
Outline TGF-b signal transduction
Type I homodimer phosphorylates Smad 2 or 3, which then dimerises with Smad4, which then enters the nucleus as a TF
What are R-Smads?
All apart from 4, 6 +7, receptor-regulated Smads
What is special about Smad4?
Co-Smad - common to all TGF-b signalling
