CellSig14 - 22 Flashcards Preview

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Flashcards in CellSig14 - 22 Deck (22):
1

What does Wnt stand for?

Amalgam of Wingless and int

2

What is the relationship between Hh and Wnt?

Hh upregulates Wnt, Wnt controls engrailed, which controls Hh expression

3

What factors are associated as supplementary to the Wnt pathway?

Porcupine, Wntless, HSPGs

4

How does Wnt become active?

Palmitoylation then palmitoleic acid modification

5

What is porcupine?

Acyl transferase required for formation of Wnt signals

6

What is Wntless?

7TM required for transport of Wnt to PM, maybe even release

7

Describe Wnt release

Hydrophobic, so may form multimers or loaded onto lipoprotein particle

8

What binds Wnt?

Frizzled/LRP

9

What nuclear factor responds to Wnt?

Beta catenin/armadillo gene

10

What is LRP?

LDL receptor related protein

11

Where does Wnt bind?

N-terminal of Fz - CRD (cysteine rich domain)

12

Characterise LRP

1TM that contacts Wnt

13

What is the most important EC Wnt inhibitor?

Dickkopf1 (Dkk1)

14

What does Dkk1 do?

Binds LRP and Kremen, promoting internalisation of LRP

15

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.

16

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.

17

What is required for beta-catenin destruction?

Phosphorylation by CK1 x1 AND GSK3b x3

18

What does phosphorylation of beta-catenin form the binding site for?

bTRcP/Slimb

19

What other components may aid TCF/beta-catenin transcriptional activation?

Legless and Pygopus

20

What alternative pathways is Wnt used in?

Planar cell polarity direction and convergent extension movements

21

What is Wnt involved in?

Drosophila segmentation and D/V wing disc formation, C. elegans neurblast migration, vertebrate organiser formation

22

What human specific systems is Wnt involved in?

Maintenance of crypt stem cells, cancers