>>Dr. Ketchum: Here we will continue our discussion
of second messenger systems. And so remember we’re still talking about G protein-linked
receptors, and now we’re going to be talking specifically about DAG, IP3, and calcium.
So these are all considered second messengers. And so on this one figure, you have all three
second messenger systems in one diagram. You’re going to see a lot of similarities across
these second messenger systems, and there’s also some connectivity between the second
messenger systems as well. Once again, we’re going to begin with the ligand that binds
to the receptor. So then once the ligand binds to the receptor, then that will activate your
G protein. So once again, GDP falls off the alpha subunit. GTP binds to the alpha subunit,
and that activates the amplifier enzyme called phospholipase C. Phospholipase C can be abbreviated phospholipase
C. Then once phospholipase C is activated, that will convert PIP2 to IP3. Now PIP2 is
a phospholipid. So once it gets converted to IP3, IP3 then is released into the cytoplasm.
IP3 then binds to a channel on the endoplasmic reticulum. So this is the plasma membrane
of the endoplasmic reticulum. IP3 binds to this channel on the endoplasmic reticulum,
the channel then opens. And when the channel opens, calcium—there’s high concentration
of calcium here inside of the endoplasmic reticulum—calcium will leave via the channel
and enter into the cytoplasm. So this green ball is calcium. So calcium, remember, is
also a second messenger. Calcium can automatically cause a response inside of the cell, such
as skeletal muscle contraction, which you’ll learn the mechanism for that later. Or, calcium
can bind to calmodulin. And this is just dependent on what type of tissue type you’re in. If
calcium binds to calmodulin, that activates… protein kinase. Protein kinase then, as we all know
now, phosphorylates a protein. And when you phosphorylate a protein, you get some sort of
response inside of the cell. That’s the IP3 and the calcium second messenger system. Now let’s look at DAG. So the ligand binds
to the receptor, you activate your G protein, it activates your amplifier enzyme called
phospholipase C. Now PIP2, rather than being converted to IP3, PIP2 gets converted to DAG.
This is also a phospholipid. DAG is also a second messenger. So it’s in the membrane—it’s
a phospholipid in the membrane. That then will activate protein kinase C. Remember when
we talked about the cyclic AMP second messenger system? Cyclic AMP activated PKA: protein
kinase A. DAG activates PKC: protein kinase C. Protein kinase C then phosphorylates a
protein. Remember, it takes ATP to do that. So you have to hydrolyze ATP to do that, and
then you get some sort of response inside of the cell. So the question is how do we
turn off these systems? So as you might have guessed, the ligand has to fall off of the
receptor. Remember, binding is reversible. Then we deactivate—you deactivate your G
protein by hydrolyzing it. So so far, that’s the same as turning off a cyclic AMP second messenger system. We can use a phosphodiesterase to break down the second messenger. So you can
use an IP3 phosphodiesterase, a DAG phosphodiesterase to break down the second messenger, and you
can use phosphatase to dephosphorylate your protein. So the mechanism for turning off
an IP3 or DAG and calcium system is the same as turning off cyclic AMP. So that concludes
our discussion of the IP3, DAG, and calcium second messenger systems.
