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Components of Hedgehog Signalling
 Fused (Fu)
Fused is a Drosophila segment-polarity gene needed for the activation of Hh target
gene transcription. It transmits the Hh signal in imaginal discs and plays mediating
roles in Hh signalling with consequences for each of wingless expression, dpp and
engrailed (en).
Protein:
The N-terminal of the fused gene is homologous to a catalytic domain of
serine-threonine kinases. The C-terminal corresponds to a putative regulatory domain.
 Protein Kinase A (Pka)
Pka is a component needed for the repression of Hh target gene transcription.
It is a cAMP-dependent protein kinase A, a serine/threonine kinase with
effects in the repression of the Hh signal. Cyclic AMP is used in
Drosophila to transduce external signals sensed by G
protein coupled receptors such as Smoothened. Adenylate cyclase
is the presumed target of Smo in the mammalian signalling pathway.
This is an enzyme that converts ATP to cyclic AMP, leading to camp
regulating Pka. The Pka target in segmentation is currently unknown
although some research has speculated the target may be Ci.
As Pka activity is reduced, it leads to accumulation of full
length Ci (Ci-155) and to ectopic expression of Hedgehog target genes.
 Proteasome (Pro)
The role of proteasome in Hh signalling revolves around Ci as it targets
Ci for cleavage by the proteasome pathway. Pro inhibitors block the
processing of Ci in tissue culture cells. Proteins are often targeted
by due to their phosphorylation and it is proposed that Hh modulates
Ci phosphorylation.
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