So G-protein coupled receptors are where we're going
to go next. These are the largest category of
receptors in animal cells. And recall, they are
involved in metabolic and structural changes
as opposed to the receptor tyrosine kinases which
were involved in just the general daily function
of cells for the majority of the time. So as we look
at G-protein coupled receptors, we have G-proteins
involved. What are G-proteins? G-proteins are
proteins that are activated by GTP, right.
So, in this case we have a ligand and it binds to
its receptor. This is the first messenger.
And that receptor is going to activate a G protein.
And the G protein goes somewhere else entirely
to activate another effector protein. That effector
protein is often embedded in the membrane
and that effector protein will activate a second
messenger. Really what we're doing here again is
passing on phosphates to activate proteins
further and further down in the cascade.
As we activate that second messenger, it can run
out and activate all kinds of kinases
to have all kinds of cellular effects. So a general
example of how this work seems pretty similar
doesn't it to the receptor tyrosine kinase cascade.
Although it's different in its specifics.
Now we're ready to look at some specific second
messenger systems. First of all, keep in mind
that the G-protein is the piece that links the
receptor that's embedded in the membrane
to the effector protein which is also often embedded
in the membrane. And that the effector protein
is what produces the second messenger that runs off
and has all the effects throughout the rest of the cell.
So first, a cyclic AMP second messenger system that's
mediated by adenylyl cyclase. Adenylyl cyclase
is the effector protein and cyclic AMP is the
second messenger. Here you have a receptor
for a molecule. The molecule binds to the receptor
and activates a G-protein. In this case,
the G-protein has three subunits. And it's the
α subunit that will activate adenylyl cyclase.
The β and γ subunits have the opportunity to go off
and activate a completely different protein cascade.
So you can see that one receptor could have many
other effects but we'll stick with the
adenylyl cyclase cascade and the α subunit activating
that. Now we can activate the second messenger
where ATP comes in, drops off some phosphates and
forms cyclic AMP, adenosine monophosphate.
Adenosine monophosphate is the second messenger in
this system. And it will go on to activate
protein kinase A. We shorthand that as PKA. Protein
kinase A is activated and that will go on to
activate many more proteins perhaps with some signal
amplification and we'll have our cellular response.
The cellular response depends on what other proteins
are activated. So, it could be different
but this mechanism comes into play multiple times
throughout Biology. So it's a very popular
signalling system so to speak. Let's now look at
phospholipase C, another G-protein mediated pathway.
In the case of phospholipase C, we have that as the
effector protein. This effector protein though
activates a couple of other second messengers. So
in the phospholipase C system the signal molecule
ligand binds to the receptor. Activates the same
sort of G-protein which has three subunits.
We've got α, β, γ. α also can activate the
phospholipase C. And PIP2 is a protein.
It's a shorthand for protein that is going to be
the substrate giving phosphates to this adenylyl cyclase.
And it's going to form diacylglycerol
as well as inositol triphosphate or IP3.
And these two second messengers are now able to
activate a variety of cellular processes.
In this case, IP3 is going to activate the release
of calcium from the endoplasmic reticulum.
If we're in a muscle cell, it's the sarcoplasmic
reticulum. But either way we're going to release
calcium which is going to result in muscle contraction.
However if this system is happening in an
endocrine cell, it's not interested in having any
muscle contraction, it's interested in releasing
hormones. So this very same signalling mechanism
with IP3 is going to allow release of hormones
from hormone producing cells such as the pituitary
gland or adrenal gland. Different proteins
can have different effects in different cell types.
So, let's say that you need to run away from a big
mountain lion. Probably not the best idea but if you
need to get out of there, we're going to activate
the fight or flight system, right. Epinephrine or
adrenaline is present and we need some sugar
to get away. This is an example where two different
signal molecules act on the same pathway
having the same effect. So, epinephrine binds to its
membrane receptor and a G-protein activates
the second messenger. And glucagon involved in
releasing sugar also binds to its receptor
and has the same effect. So both of these signal
molecules are binding to different receptors
yet having the same effect inside the cell. On the
contrary, we can see that one signal molecule
could have very different effects. For example, in
this case epinephrine. We're trying to run away again.
We need to increase our heart rate but we are not
interested in digesting food at this point in time.
So epinephrine will end up in the heart muscle creating
adenylyl cyclase that increases the production of
cyclic AMP, the second messenger. And the cyclic AMP
increases the contraction strength. So that's the
effect for the full cells there. But while we're still
running from this mountain lion, we have our gut
and we do not really need to be putting a lot of
energy into digesting food at this particular moment.
So, a different G-protein modulates this process in
which we see that G-protein inhibiting
adenylyl cyclase. So grabbing on to that enzyme and
stopping it producing cyclic AMP, and so then
we have relaxation of those muscle cells. So one
signal molecule having different effects in
different cells or you could have multiple signal
molecules having the same effect in the same cell.
So it's a very diverse system of
cell communication and control of cell functions.