NOTCH, Wnt and Hh signaling

Question 1

Why are these signaling pathways essentially irreversible?

Answer 1

Because they are switched on by protein degradation

Question 2

What are the ligands for the NOTCH receptor?

Answer 2

Delta/Serrate/Jagged

Question 3

Describe NOTCH signaling pathway in brief

Answer 3

Notch receptor cleaved from Golgi and translocates to cell membrane.
NOTCH comes into contact with neighbouring cell if producing Delta ligand
NOTCH binds Delta ligand on neighbouring cell and the NOTCH is cleaved, leaving transmembrane and intracellular domains behind
The remaining domains are then cleaved twice by a protein called Presenilin.
Fragments travel to nucleus and bind to transcription factors.

Question 4

Briefly describe wingless signaling

Answer 4

Wingless activates receptor frizzled.
Frizzled activates protein dishevelled, which locates to the membrane.
Dishevelled inhibits AXIN APC GSK3 and CK1.
Without dishevelled inhibiting these proteins they would target B-catenin for degradation
When wingless is present, B-catenin is protected from degradation and can go on to activate transcription of Wnt target genes

Question 5

Briefly describe Hedgehog signaling

Answer 5

Hedgehog (protein ligand) binds to the receptor patched.
Hedgehog binding to Patched causes proteolysis of the receptor.
In the absence of Hedgehog, patched inhibits the protein smoothened.
With hedgehog present, smoothened is not inhibited and can protect Ci from cleavage.
Smoothened binds proteins which would hyperphosphorylate and subsequently target Ci for ubiquitination preventing their action.
Non-cleaved Ci is a transcriptional activator for Wnt