Another important function performed by proteins
is that of signaling. Now signaling is also
known as communication and I’d like to think
about it as the way that the cell responds
to its environment, especially in a multicellular
organism this is very important. It's important
for all of the different tissues of the organs
to be pulling the oars at the same time and
not countering each other. The liver has specialized
functions for example, to control the amount
of glucose and fat and so forth that's released
into the bloodstream. So it's important that
the liver be able to respond to and hear signals
that other cells in the body telling it about
the need for various nutrients, so this signaling
is very, very important.
Now there are several different levels of
signaling and several different proteins that
are involved in the signaling process. In
fact there are many proteins involved, because
there are many different signaling processes,
but I’m going to talk about them here in
very general terms. So the first level I want
to talk about are the membrane receptor proteins.
Now these play an absolutely critical function
because it's through these proteins that the
signal must be transmitted from outside of
the cell to inside of the cell. Now that is
absolutely essential, if my liver cell and
the rest of the body is telling me I need
glucose, that information has to get inside
the cell, where the glucose can be made and
released, for the body to have the glucose
that it needs, so that transmission of information
happens through a membrane receptor. The membrane
receptor proteins are what we call integral
proteins, that is they are embedded in the
lipid bilayer as you can see in the figure
on the right. They are surrounded by the lipid
bilayer in fact, with a part of them projecting
above it, in this case meaning outside of
the cell, and part of it projecting below
it, in this case inside of the cell.
The membrane proteins themselves are known
as 7TMs and the TM stands for transmembrane.
So as we look at this illustrative figure
on the right, this protein has seven different
coil domains and they are actually numbered
on there but they are a little hard to see.
The seven different coil domains that are
going back and forth across the lipid bilayer
and that going back and forth with these different
domains occur seven times. Many of the proteins
are 7TMs, and 7TMs is actually a common category
of membrane proteins.
The membrane receptors bind to what's called
a messenger molecule. So that messenger molecule
is being sent by other cells in the body.
The messenger molecule binds to the receptor
protein on the outside of the cell, and that
binding to the receptor causes the receptor
to change shape on the inside of the cell.
Then that change on the inside of the cell
causes everything else to happen. The things
that happen on the inside of the cell usually
results in the formation of what's called
a second messenger, and we’ll see that in
just a little bit.
Another important function in the signaling
process is that of peptide hormones. Now I've already
described the first messengers that are released
by cells to go to the target cell to bind.
Those hormones are oftentimes proteins themselves.
These are released and made by the endocrine
system. And some examples of these peptide
hormones include insulin, which is very commonly
known, oxytocin, and glucagon among many others.
Inside the cell, there are proteins that play
very important roles in communicating that
information that has come in from the outside.
Now these proteins can have a variety of different
functions, but one of the very common functions
that many of them have is that they are kinases.
What kinases do is they put phosphates onto
other proteins. So it’s actually a cascade of kinases
that can happen, one protein phosphorylating
another protein, which causes that protein
to become active and phosphorylate another
protein, and a signal is communicated from
one protein to another as result of this kinase
action. That’s only one example, there are
The last important function I want to talk
about that proteins play in the signaling
process is that of functioning as transcription
factors. Transcription of course is the process
whereby information in DNA, is transferred into
messenger RNA in the process of transcription.
The ability of RNA polymerase to start the
synthesis of RNA is a function of proteins
that tell it where to start synthesis. Transcription
factors play a role in this process, they
can either turn on transcriptions of specific
genes or turn off transcription of specific
genes, depending upon the actual function.
As a result of all the signaling events and
signaling proteins that happen, a cell can
then respond to the outside signal in the
way that the body needs it to respond. Whether
it is releasing nutrients, whether it's telling
it to divide, or whether it's telling it to
do other things that might be beneficial.
This slide actually illustrates the signaling
process for a liver cell. Now it doesn't show
the transcription that I talked about before,
but it shows many of the other steps in the
process. In this slide we can see at the top
left, a protein that's embedded in the membrane
that’s actually the signaling protein. It
is called the beta-adrenergic receptor. And
as you can see it's a 7TM, that is, it has
seven domains crossing the lipid bilayer.
On the right bottom of the beta-adrenergic
receptor, we can see an interesting protein
that has three units, an alpha unit, a beta
unit and a gamma unit. And that alpha, beta,
gamma is part of what we call a G-protein.
That G-protein has an important function and
it’s carrying a nucleotide called GDP. In this
state it's not active, it's not stimulating
any process, but when the adrenergic receptor
binds to the hormone from outside of the liver
cell, the receptor changes its shape and that
change in shape causes a change in the G-protein.
The change in the G-protein causes a couple
of things to happen. First of all, the G-protein
releases the beta and the gamma as it binds
a GTP in place of the GDP. When this happens,
the G-protein then moves over to an enzyme
that is also embedded in the membrane called
adenylate cyclase. What adenylate cyclase
does when it’s stimulated by this G-protein,
is it causes the formation of a molecule called
cyclic AMP, that's converted from ATP as you can
see here. Now cyclic AMP is a molecule that we call
the second messenger. The first messenger
was the hormone outside of the cell that caused
the receptor to be activated. The cyclic AMP on
the other hand is an internal molecule that
is going to activate an enzyme. The enzyme
that gets activated by cyclic AMP is protein kinase
A, and protein kinase A is one of those kinases
I talked about. It phosphorylates another
enzyme called phosphorylase kinase and in
the process causes that enzyme to become activated,
where it previously was inactivated. The phosphorylase
kinase in turn, phosphorylates another enzyme
called glycogen phosphorylase B, converting
it into glycogen phosphorylase A. At that
point the glycogen phosphorylase A is active,
and that glycogen phosphorylase A then breaks
down glycogen to produce molecules of glucose.