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0:04
Welcome back from the break.
We're now going to talk about,
how does Wnt signal?
0:11
We understood a lot about
the genes in the Wnt
pathway from flies.
Where we saw
porcupine, wntless,
frizzled, dishevelled,
zeste-white 3,
armadillo, and Tcf.
When it became clear that
it is also important in cancer,
there's a lot of interest in
looking at it in
the human system.
Then it turned out
that there was
a very good alignment
between flies and mammals.
Flies have wingless,
humans have Wnt.
Same gene, different names.
Then there's frizzled,
dishevelled,
a kinase which in
vertebrates is GSK3,
β-catenin, and then
the transcriptional
repressor Tcf/Lef leading to
β-catenin regulated
transcription.
1:00
In its basic form,
Wnt/β-catenin signaling
is pretty simple.
I've already told you,
Wnt bind to receptors at
the cell surface that sets
up a signaling cascade
that stabilizes the
β-catenin protein which then
moves to the nucleus and
turns on important genes.
That's a really simple model.
Of course, it's
never that simple.
We call this simple model
the canonical pathway.
1:27
This simple model has
a few more details,
where you can see GSK3,
Casein kinase 1α, Axin,
APC, and β-catenin form a
complex in the cytoplasm.
This complex has been called
the β-catenin destruction
complex because
that's its job—to
cause degradation of
β-catenin that has
left the membrane.
Now, I told you the Wnt
pathway is simple and
the canonical view of
the pathway is indeed simple
but life is complicated.
