CellSig14 - 22 Flashcards
What does Wnt stand for?
Amalgam of Wingless and int
What is the relationship between Hh and Wnt?
Hh upregulates Wnt, Wnt controls engrailed, which controls Hh expression
What factors are associated as supplementary to the Wnt pathway?
Porcupine, Wntless, HSPGs
How does Wnt become active?
Palmitoylation then palmitoleic acid modification
What is porcupine?
Acyl transferase required for formation of Wnt signals
What is Wntless?
7TM required for transport of Wnt to PM, maybe even release
Describe Wnt release
Hydrophobic, so may form multimers or loaded onto lipoprotein particle
What binds Wnt?
Frizzled/LRP
What nuclear factor responds to Wnt?
Beta catenin/armadillo gene
What is LRP?
LDL receptor related protein
Where does Wnt bind?
N-terminal of Fz - CRD (cysteine rich domain)
Characterise LRP
1TM that contacts Wnt
What is the most important EC Wnt inhibitor?
Dickkopf1 (Dkk1)
What does Dkk1 do?
Binds LRP and Kremen, promoting internalisation of LRP
Outline events in the absence of Wnt
Beta catenin phosphorylated by CKIa and GSK3b, recognised by Slimb, then ubiquitinated and degraded. TCF associate with Groucho, a repressor.
Outline events in the presence of Wnt
Dishevelled recruited to frizzled, and inactivates destruction complex, Slimb is lost. Beta catenin now accumulates and translocates to nucleus, displacing groucho, activating TCF.
What is required for beta-catenin destruction?
Phosphorylation by CK1 x1 AND GSK3b x3
What does phosphorylation of beta-catenin form the binding site for?
bTRcP/Slimb
What other components may aid TCF/beta-catenin transcriptional activation?
Legless and Pygopus
What alternative pathways is Wnt used in?
Planar cell polarity direction and convergent extension movements
What is Wnt involved in?
Drosophila segmentation and D/V wing disc formation, C. elegans neurblast migration, vertebrate organiser formation
What human specific systems is Wnt involved in?
Maintenance of crypt stem cells, cancers
