CellSig14 - 22 Flashcards

1
Q

What does Wnt stand for?

A

Amalgam of Wingless and int

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2
Q

What is the relationship between Hh and Wnt?

A

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

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3
Q

What factors are associated as supplementary to the Wnt pathway?

A

Porcupine, Wntless, HSPGs

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4
Q

How does Wnt become active?

A

Palmitoylation then palmitoleic acid modification

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5
Q

What is porcupine?

A

Acyl transferase required for formation of Wnt signals

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6
Q

What is Wntless?

A

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

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7
Q

Describe Wnt release

A

Hydrophobic, so may form multimers or loaded onto lipoprotein particle

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8
Q

What binds Wnt?

A

Frizzled/LRP

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9
Q

What nuclear factor responds to Wnt?

A

Beta catenin/armadillo gene

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10
Q

What is LRP?

A

LDL receptor related protein

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11
Q

Where does Wnt bind?

A

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

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12
Q

Characterise LRP

A

1TM that contacts Wnt

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13
Q

What is the most important EC Wnt inhibitor?

A

Dickkopf1 (Dkk1)

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14
Q

What does Dkk1 do?

A

Binds LRP and Kremen, promoting internalisation of LRP

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15
Q

Outline events in the absence of Wnt

A

Beta catenin phosphorylated by CKIa and GSK3b, recognised by Slimb, then ubiquitinated and degraded. TCF associate with Groucho, a repressor.

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16
Q

Outline events in the presence of Wnt

A

Dishevelled recruited to frizzled, and inactivates destruction complex, Slimb is lost. Beta catenin now accumulates and translocates to nucleus, displacing groucho, activating TCF.

17
Q

What is required for beta-catenin destruction?

A

Phosphorylation by CK1 x1 AND GSK3b x3

18
Q

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

A

bTRcP/Slimb

19
Q

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

A

Legless and Pygopus

20
Q

What alternative pathways is Wnt used in?

A

Planar cell polarity direction and convergent extension movements

21
Q

What is Wnt involved in?

A

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

22
Q

What human specific systems is Wnt involved in?

A

Maintenance of crypt stem cells, cancers