Membrane Bound Receptors and Secondary Messengers - Online Tutor, Practice Problems & Exam Prep

Hormones, particularly amino acid-based ones, induce cellular responses by binding to specific receptors, often G protein-coupled receptors (GPCRs). This initiates signaling cascades, such as the cyclic AMP (cAMP) pathway, which amplifies the signal through multiple steps, activating enzymes like adenylate cyclase and protein kinases. Different target cells respond variably to the same hormone due to distinct receptors and secondary messengers, leading to diverse physiological effects, such as vasodilation or vasoconstriction, depending on the context and cellular environment.

G Protein-Coupled Receptors

Hormones induce changes in target cells because those target cells have a very specific receptor for that specific hormone. But we've said these receptors can work differently because we have different types of hormones. Steroid hormones can pass through the cell membrane. Most amino acid-based hormones cannot pass through the cell membrane. So now we want to think specifically about these amino acid-based hormones. How can it induce a change inside the cell if the hormone itself has to stay on the outside of the cell? To do that, we're going to talk about second messenger systems, and specifically we're going to talk about G protein-coupled receptors. Alright. G protein-coupled receptors, or we can also just write GPCRs. GPCRs, this is a class of membrane-bound receptors that initiate signaling cascades. And I want to come back to this word cascades in just a second. But first, I just want to say it's a class of membrane-bound receptors. This is a huge group of proteins, and actually, most of them are not involved in hormone signaling. G protein-coupled receptors are the opsins in your eyes. They're what recognize scents in your nose. They bind to neurotransmitters in the nervous system. They're used all over the body. In fact, roughly 5% of the genes in your genome code for G protein-coupled receptors. Now we're talking about the details here because for understanding how hormones induce changes in cells, it's really important to understand how these GPCRs work. Alright.

So now this word cascade. We say that they're going to initiate these signaling cascades. Well, a signaling cascade, you can think it's like a waterfall. Right? So as it goes, it picks up speed. It picks up more stuff with it, and it sort of gains momentum. It gains speed as it goes. So we're gonna say a signaling cascade is when chemical messengers are linked in series. There are all sorts of different types of signaling cascades, but here we're gonna talk about the cyclic AMP or cyclic adenosine monophosphate signaling cascade, and we can write that just as cAMP. That's typically how we'll write it. The cyclic AMP signaling cascade is one of the most common examples of a signaling cascade. If you have to learn the details of one signaling cascade, it's almost certainly going to be the details of this cyclic AMP cascade. So with that, let's look at the details.

Alright. So we have this illustration down here, and just to orient you, we have the cell membrane. And above the cell membrane up here, that's going to be outside the cell, and below the cell membrane will be inside the cell. Well, we're talking about hormone signaling. So we have all these molecules that are drawn around here. We'll go through them all one by one, but the first one we want to look at is this molecule right here. That's the hormone, and that's epinephrine drawn out. Just to be clear, it's drawn a lot bigger than it would be. It's not really to scale, but for illustrations, this works. So we have this hormone. It's outside the cell, it can't cross a cell membrane, so it's going to bind to this receptor that we see here in blue. And this receptor is going to be a GPCR. So this GPCR, this blue receptor here, you can see it's bound to the hormone, but it's a big protein. It goes all the way through the membrane, and so it's able to transmit the signal across the membrane.

Alright. So that brings us down to number 2 here. It says that our receptor, or our GPCR, it's going to activate a G protein. And the G protein, you can see here, we have illustrated as this green protein right there, sort of attached to that GPCR there. Well, G protein, that's where that gets its name, the G protein-coupled receptor. Because the way this is going to work is when it's activated, it's going to replace GDP on the G Protein with GTP. GTP, well that's very similar to the molecule ATP. Adenosine triphosphate is ATP. Guanosine triphosphate is GTP. So this is a high-energy molecule. And GDP, well that's very similar to ADP. Again, adenosine diphosphate. This is guanosine diphosphate. So here we're just replacing this lower energy GDP with a higher energy GTP, and that's going to activate this G protein.

And now we can go over to number 3. Once activated, it gets released from this GPCR and the G protein diffuses along the membrane. So you can see here we have it diffusing along the membrane. These G proteins are proteins, but they have a hydrophobic portion that's inserted in the membrane, so they're stuck on the inside of the cell there. They're stuck right up against the membrane. So it diffuses across the membrane until it binds to and activates the enzyme. And we have this enzyme drawn here in pink it bound to, and that enzyme is going to be adenylate cyclase. Alright. Adenylate cyclase. So that brings us up to number 4. When adenylate cyclase is activated, adenylate cyclase's job is to convert ATP, that high-energy molecule in the cell, to cyclic AMP, or as I'm writing here, cAMP. And we can see that illustrated down here. Here we have an ATP molecule with the adenosine and three phosphates, and it interacts with adenylate cyclase. And then on the other side here, we have this cyclic AMP, cyclic adenosine monophosphate. So we can still see the adenosine but it now has one phosphate on it. It's called cyclic because this phosphate is actually bound to the adenosine in two places making a little ring. Now that's probably more biochemistry than you really need to know, but if you're wondering where the name comes from, that's where it comes from. Now real quick, helping you remember adenylate cyclase. Well, adenylate, well, you can remember it interacts with cyclic adenosine monophosphate. And then cyclase, well, it makes cyclic AMP. So what that enzyme does is right there in the name, and it lines up with the word that you need to know for what it produces.

Alright. So now this adenylate cyclase is making a whole bunch of cyclic AMP. That means we can go over to number 5. Cyclic AMP, now this is just in the cytoplasm, and it is going to bind to the enzyme protein kinase A. Protein kinase A. And protein kinase A, well it's a kinase, and kinases' jobs are to phosphorylate other proteins. So now this is an enzyme that, again, it's in the cytoplasm, and it's going to go around our kinase here. We're going to go down to number 6. This kinase is going to phosphorylate proteins, and as it phosphorylates proteins, it's turning proteins on or off, and that is going to cause or trigger our cellular response. Now it's going to turn on all sorts of different proteins depending on what the target cell is, and those proteins then go on and can do all sorts of things. Again, depending on what the hormone is, depending on what the target cell is, and that is what gives you our cellular response. So again, we started with this hormone outside the cell, and now we have a response coming from this kinase on the inside itself.

Alright. I said if you need to know the details of one signaling cascade, it's likely gonna be this one. I realized that I've sort of thrown a bunch of vocab at you here and put it in a very specific order that might be a little tough to remember. So we've put together a little memory tool for you here. And so to help remember this, we have this camper, and this guy is sitting at a campfire roasting a marshmallow, and it says that he is at camp kinase. Alright. And our memory tool is holding really great activities at camp kinase. Alright. Let's go through this. So remember, the first step is the hormone comes in, and that hormone well, we have the letter H for holding. The hormone binds to a receptor. The receptor we have R in the word really. The receptor activates our G protein. The G protein, well, that's the "G" in great. The G protein activates adenylate cyclase. Well, adenylate cyclase that matches up with the letter "A" in activities. Adenylate cyclase produces cyclic AMP or as we write it cAMP. Well, that's just the word camp. Cyclic AMP activates a kinase and, well, we're at CAMP Kinase. So again, holding really great activities at CAMP Kinase that matches up with the hormone activating the receptor, which activates the G protein, which activates adenylate cyclase, which produces cyclic AMP, which activates our kinase. Alright. We're going to talk about this in more detail going forward because, again, we said that this is a cascade, and I said as part of a cascade is that it can get bigger as it goes. So one thing we want to talk about is how do we start with just a few hormones and end up with a massive cellular response? So we're going to talk about that. And we also just want to know, I said if you need to know one, it's likely this one, but there are others. So we just want to see how different signaling cascades can produce different responses, and so we'll compare some in that way. I'm looking forward to it. I'll see you there.

Membrane Bound Receptors and Secondary Messengers Example 1

Our example gives us the steps of a signaling cascade, and it wants us to put them in order by writing the correct letter on the blanks here. So, before we do this, remember, we had a memory tool for remembering the cyclic AMP signaling cascade. I'm going to write that out first. My memory tool was "Holding really great activities at camp kinase". The first letter of each one of those words matches up with one of the major players, one of the molecules in each one of these steps. So, as we go through, we see the order here is going to start with a hormone binds an extracellular receptor. Well, that's our first two letters here with the hormone binds a receptor binds to a receptor. I'm going to cross those out because we already have those down. And then we're going to say, well, from the receptor, we go to something with the 'g'. The receptor activates a G protein. So, I think that's going to be my next step. And there it is. C, the G protein, is activated. So, I'm going to put C on the line here, and I just cross this out to keep things organized.

Alright. So then we go from our G protein to something that starts with an 'a'. Remember, the G protein activates adenylate cyclase. Alright, and adenylate cyclase is activated. That's right there. That's option D. So, I'm going to put D on the next line, and I'm going to cross this out again just to keep things organized. Alright, so now our adenylate cyclase enzyme is activated and adenylate cyclase is going to go to cAMP. Well, cAMP stands for cyclic AMP, so adenylate cyclase is going to produce cyclic AMP and that's option B here. ATP is converted to cyclic AMP. So I'm going to write B on my next line, cross this out down here just to stay organized, and then finally, cyclic AMP is now in the cytoplasm, and it's going to go bind to a kinase. Alright. Well, look at that. Our option here a protein kinase is activated. It's activated when cyclic AMP binds to it. So, that's going to be A is next and the kinase is going to go out. Kinase phosphorylates protein, so it's going to phosphorylate all sorts of proteins and that's going to lead to our cellular response. And we did it. We got from a hormone that can't cross the cell membrane. It's stuck on the outside of the cell. We went through this signaling cascade using secondary messengers to initiate a cellular response. That's how we do it.

What is the role of G proteins in GPCR signaling?

• A. Catalyzing DNA synthesis.
• B. Initiating apoptosis.
• C. Transcription of mRNA.
• D. Activating downstream effectors.

Amplification

An amino acid-based hormone typically induces a response in a cell by binding to a receptor on the outside of the cell, often a GPCR (G-protein coupled receptor), and initiating a signaling cascade inside the cell. And we said that the word cascade is meant to evoke something like a waterfall, where it's picking up speed, picking up momentum, getting bigger as it goes. That idea of getting bigger as it goes, we're going to call amplification, and we're going to look at that in more detail here. So first, let's just remember that a signaling cascade is this series of linked chemical messengers where they pass the signal off from one to another, and we looked at an example of that when we looked at this cyclic AMP signaling cascade.

Well, this idea of amplification is going to be when one molecule in that pathway passes the signal to multiple molecules and that's going to increase, we'll signify that with an up arrow, the total amount of signal. Now when we looked at how that cyclic AMP pathway works, we just said, you know, this molecule activates the next molecule, but there's going to be times when it activates actually multiple molecules, and we're going to illustrate that using these sort of personified happy little molecules here. And these are the molecules of the cyclic AMP signaling pathway. And here, they're all holding a cell phone and they're sending a message from one to another, a text message or a DM or something like that. And we're going to say there's going to be a couple of key places in this pathway where the signal is amplified. We're going to say that the cyclic AMP secondary messenger systems are amplified when, and then we have three specific places here.

Let's take a look. We're going to start with our happy little hormone here. The hormone starts the signal by sending a message to the GPCR, this blue GPCR here, but it sends that signal by actually physically binding to the GPCR. And a hormone can only bind to one GPCR at a time, so we're not going to get any amplification here. But that GPCR is going to activate multiple G proteins. And so our next little figure in the line here, this green G-protein, well this GPCR is going to get the signal, but it's actually going to pass it off to multiple G proteins. Now these G proteins have the message and they're going to go out and diffuse across the membrane and they're going to pass the message off to their friend here, adenylate cyclase that we see in pink. We'll label that as AC. But again, G proteins have to actually bind to adenylate cyclase, and adenylate cyclase is only active when the G-protein is bound to it. So again, we're not going to get any amplification. Each G-protein just sort of sends this message off to one adenylate cyclase. But adenylate cyclase is an enzyme, and so it's catalyzing chemical reactions really, really fast. So adenylate cyclase produces many, many cyclic AMP molecules. So here, adenylate cyclase is going to send this message on to the cyclic AMP that we see here. But again, it's going to amplify because it's sending it to each individual adenylate cyclase, it's sending that message to many. It's making many cyclic AMPs.

Well, cyclic AMPs are going to send the message off to its little blue friend here, a kinase. But again, cyclic AMP acts actually have to bind to the kinase for the kinase to be active, and you actually need a few cyclic AMPs bound to the kinase for it to work. So you're not going to get any amplification here again. It's going to stay relatively the same. But again, our kinase, our kinase is an enzyme, so protein kinase is going to phosphorylate many, many proteins. So you can see already, from one hormone, we have many kinases, and those kinases are now going to go out and phosphorylate whole bunches of proteins. And then those proteins, some of those are going to go off and activate even more molecules. So we can start with very few hormones. Here we have one, but, like, a countable number of hormones binding to receptors on a cell, and that can, in turn, induce this change that results in literally millions or billions of molecules being activated inside the cell, and that can induce a huge physiological response. So again, this process of amplification, because at certain steps in this process, the message gets amplified, it gets sent on to multiple molecules, you can have a very low hormone signal induce a very large physiological change. Alright. We're going to practice that more in examples and practice problems of fall. You should give them a try.

Membrane Bound Receptors and Secondary Messengers Example 2

In this example, it says the image below shows a signaling cascade using cyclic AMP as a second messenger. We want to circle the places on the image where amplification can happen, and we see this image here that we've seen before showing our cyclic AMP signaling cascade. Now, one tricky thing here is that this image isn't labeled. So the first thing I want to do is write down the molecules involved so I can label them or at least label them as we go. Remember, we have that memory tool for that. I said holding really great activities at camp kinase. Alright. So our first thing that happens, we have the hormone and the receptor. The hormone binds to the receptor. So here we have the hormone, and it's binding to this blue receptor here, which I'm going to label as a GPCR, a G protein-coupled receptor. Alright. Can we have amplification here? Well, one hormone can only bind to one receptor at a time, so we're not going to get any amplification at this step. So next, what happens? Well, now the GPCR is activated. It's bound to the hormone, so it's going to pass the signal on to this G here. And this G is going to be our G protein that we see in green, It's going to activate the G protein. Can we have amplification here? Absolutely. Alright. This GPCR can actually modify multiple G proteins and activate them. So as long as that hormone is bound to the receptor, it can continue activating G protein. Now this G protein is going to go along to our next thing, A. So it's going to diffuse across the membrane here, remember, and it's going to bind to this enzyme A, and A stood for adenylate cyclase, which I'll label as AC here. And so, do we have amplification at this step? Well, with the G protein binding to adenylate cyclase, well, one G protein can only bind to one adenylate cyclase at a time, so we don't get amplification, and that adenylate cyclase is only active when it's bound to the G protein. So no amplification there. Our next step, we're looking at this cyclic AMP. So here we have the ATP being converted into cyclic AMP. Can we get amplification there? Absolutely. This adenylate cyclase, this is an enzyme, so it's going to catalyze this reaction that converts ATP into cyclic AMP, and it can catalyze it very quickly. So it's making a whole bunch of these cyclic AMP molecules. Well, the cyclic AMP molecules then go out and bind to a kinase. So here's our kinase. Are you going to have amplification at that step? Well, not at the step of the cyclic AMP binding to the kinase because, again, the kinase is only active if it's bound to cyclic AMP, so the cyclic AMP can only bind to one kinase. But remember here, we'll label our kinase. What does the kinase do? A kinase phosphorylates other proteins, and it can do that pretty quickly. So I'm actually going to draw some arrows coming out of the kinase because this is phosphorylating other proteins resulting in our cellular response, and that is another place that we can definitely see amplification. Alright. So again, amplification, we can start with one or just a few hormones signaling to the cell, And because at these steps, we can get multiple molecules getting the signal passed to them, we can amplify the signal and we can end up with a very large cellular response from those kinases in the end. Alright. Four problems to follow. I'm going to try.

Hormones can bring about substantial physiological changes at very low concentrations. How does this relate to the concept of second messenger systems?

• A. Second messenger systems act more quickly, creating a larger cellular response.
• B. Second messenger systems modify the DNA directly, allowing the hormone to make an impact even at low concentrations.
• C. Second messenger systems prevent hormones from being degraded so they can exert their effect for a longer duration.
• D. Second messenger systems amplify the original hormone signal, allowing it to work at low concentrations.

Secondary Messengers

Whether or not a hormone induces a change in a cell depends on whether that cell is a target cell, and whether or not it's a target cell depends if it has the correct receptor for that hormone. But different target cells will respond differently to the same hormone. And so here, we want to really break down how and why that works. We're going to do that by talking about signaling using different secondary messengers. Now we've already introduced the second messenger, cyclic AMP. We're going to review that here, but we're also going to add a little twist to it. And then we're also going to talk about the second messengers, DAG and IP3. So, we'll start by saying that hormones may induce different signaling cascades depending on a few things here. First, the presence of a specific receptor. Now, here, we're still talking about these GPCRs, these G protein-coupled receptors. But one hormone might actually bind to several different G protein-coupled receptors, and these different GPCRs are going to be used by different cells, and the different GPCRs will cause a different signaling cascade inside the cell. Now, one of the main things that can be different for these signaling cascades is the second messenger used. So depending on what the second messenger is in the cell, that's going to turn on or turn off different things in the cell and you'll get a different response. Now, even further down the line, we have the activity of the kinase. Often, what happens in these signaling cascades is that a kinase gets activated, and kinases go out and phosphorylate different proteins. But we may activate different kinases, and even the same kinase may have different effects in different cells. And that's just because different cells have different proteins. So, for example, the same kinase in a cardiac cell versus a liver cell is going to have a different cellular response because those cells just have different proteins inside of them. Alright. Now, to break this all down, let's go through these different signaling cascades. We'll start with the one we know, the cyclic AMP signaling. So this starts with a hormone. That hormone binds to a GPCR, that G protein-coupled receptor. The GPCR activates a G protein. The G protein diffuses across the membrane, binds to adenylate cyclase. Adenylate cyclase is then activated. When it's activated, it converts that ATP into cyclic AMP. Cyclic AMP then binds to protein kinase A. And we have several arrows coming off the bottom of that protein kinase A because it's going to go out and it's going to phosphorylate a whole bunch of different proteins in the cell, and that's going to cause that cellular response. Well, here we've talked about making cyclic AMP, but another response the cell may do is to inhibit, or we're going to say here's cyclic AMP signaling inhibition. So to break this down, we'll start going through the same way we did. We're going to have a hormone. It might be the same hormone. It's going to go out. And in a different cell, well, it's going to bind to a GPCR, but it's going to be a different GPCR. Structurally very similar, but how it responds is going to be slightly different. It's going to respond by activating a G protein, but it's a different G protein. Again, structurally similar, but it's going to work slightly differently. This G protein is going to go it's going to diffuse across the membrane and it's going to bind to adenylate cyclase. But instead of activating adenylate cyclase, I'm going to draw a little down arrow here because it's going to block the function of adenylate cyclase. Well, if adenylate cyclase is turned off, well, that means the ATP in the cell just stays ATP. It doesn't get converted to cyclic AMP. And so we have the cyclic AMP grayed out. We're not making cyclic AMP. If we're not making cyclic AMP, the cyclic AMP can't bind to the protein kinase A, and so I'm going to draw a little down arrow here to say that we're sort of shutting off that protein kinase A, and we don't have any arrows coming off around the bottom. It's not going out phosphorylating proteins. We're causing a very different cellular response, in many ways, almost the opposite cellular response because instead of making cyclic AMP, we're blocking the production of cyclic AMP. All right. Well, we may also use just completely different secondary messengers. So here we're going to look at this DAG and IP3 signaling using these two molecules as second messengers. So again, we'll have a hormone go out. It might be the exact same hormone. It's going to bind to a GPCR, a G protein-coupled receptor. It's a different GPCR, again, structurally very similar, but a different one. It's going to activate a G protein, again, structurally similar, but a different G protein. The G protein is going to go out. It diffuses across the membrane and it binds to an enzyme, but it's a different enzyme. This time it binds to phospholipase C. And phospholipase C does something completely different from adenylate cyclase. What it does is it takes this molecule PIP2 or sometimes we just call it PIP2. Now, this stands for a much longer chemical name that almost certainly you don't need to know. We'll just call it PIP2. It takes PIP2 and it breaks it into two smaller molecules, DAG and IP3. Again, these have longer chemical names that almost certainly you don't need to know. So now we have these second messengers, DAG and IP3. Well, DAG goes out and it binds to a protein kinase, but it binds to protein kinase C, a completely different protein kinase that is now activated and it's going to go out phosphorylating proteins in the cell, but it's going to be a completely different set of proteins it's phosphorylating. IP3 is going to do something different. IP3 is going to cause the release of calcium ions from stores in the cell from places like the endoplasmic reticulum. Those calcium ions will have numerous physiological responses. A major one is that they're going to turn on, sort of through a couple of steps, they're going to turn on other protein kinases. Those other protein kinases are going to phosphorylate all different sets of proteins. Alright. So here you see you can start with the same hormone. And by just changing the GPCR that it binds to, you can get very different responses in the cell. Now to look at this, I just want to look at one example. And you almost certainly aren't responsible for the specifics of this example, but I think it's illustrative. So we're going to look at epinephrine. Now epinephrine is the same thing as adrenaline, and we've been using this hormone sort of as an example as we go. Well, epinephrine is active in the fight or flight response. So one thing that happens is that during their fight or flight response, you release epinephrine, and it's going to bind to these GPCRs called beta 2 receptors. And these beta 2 receptors are expressed in bronchial smooth muscle, and your bronchioles are the airways that go down into your lungs. Well, in these bronchial smooth muscles, the beta 2 receptors set off this cyclic AMP signaling cascade, and so I'm going to draw an up arrow here. We're going to get more and more cyclic AMP in the cell. That's going to turn on protein kinase A, and that's going to result in vasodilation. Vasodilation, those airways are going to relax, they're going to get bigger, and that makes sense for a fight or a fight response. Right? If you need to run somewhere or fight something, you want your airways nice and open so you get all the oxygen you need. It's also why epinephrine is used in an EpiPen, because if you're having an allergic response and those airways are closing down, the epinephrine will cause this response and cause them to open up again. Alright. But regardless, we have epinephrine causing one response in these bronchioles, but the same hormone will go out and it will bind to a different GPCR. These alpha 2 receptors are in arterial smooth muscle. Now this is in specific arterioles that are going towards places like your skin. And in this arterial smooth muscle, these alpha 2 receptors cause a cyclic AMP response, but this is that cyclic AMP inhibition. So I'm going to draw a down arrow there. So now we're blocking the production of cyclic AMP. Well, if you block the production of cyclic AMP, you get less protein kinase A turned on. If you get less protein kinase A turned on in these cells, you get vasoconstriction, or at least it blocks the vasodilation. And now that makes sense for blood vessels going to places like your skin. If you need to run somewhere or fight something, you don't need to worry about blood in your skin. You want it in your skeletal muscle. So you're going to squeeze down on those places where you don't really need the blood to go. Alright. But we're not done. This same hormone is going to also bind to another type of GPCR called an alpha 1 receptor. These alpha 1 receptors are in the same arterial smooth muscle cells. These alpha 1 receptors cause a completely different response. They cause this IP3 and DAG signaling response, and so here I'm going to draw an up arrow because we're getting more and more IP3 and DAG in the cell. Well, this results in a whole different cellular response, a whole different set of proteins being phosphorylated here, but it's also going to cause vasoconstriction. So, before we sort of didn't block vasodilation with those alpha 2 receptors. Now we're actively constricting. And so here we're reinforcing using a whole different signaling cascade, reinforcing that cellular response, and making sure that these blood vessels really close down. So again, we have one hormone causing 3 different signaling cascades, 2 of them happening in the same cell. And so when you think of these what are relatively simple things, a hormone, a single molecule going in the blood, how does it cause different responses in all these different cellular tissues? This is how. Alright. Like always, we have an example and practice problems to follow. You should give them a try, and I will see you there.

Membrane Bound Receptors and Secondary Messengers Example 3

My example tells me that the image below shows a part of a signaling cascade that uses IP3 and DAG as secondary messengers. We need to label each component and circle the places on the image that are different from a signaling cascade that uses cyclic AMP as a secondary messenger. Alright. So as I look down here, we have a list labeled A through H. These are the things that I need to label on my image here. And in the image, well, we have this image of a membrane and all these molecules around it with a whole bunch of blanks that I'm going to need to fill in. And I see the membrane, and just quick for reference, the outside of the cell is going to be on this side of the membrane, and inside of the cell is going to be on the bottom down here on this side of the membrane. And when I look at it, it looks very similar to what we labeled for that cyclic AMP signaling cascade, but I already see some key differences here. Now as I go through this, we've learned the cyclic AMP signaling cascade pretty well and the way I want to do it is I want to know that one really well and then remember the differences for other stuff. And I also want to do that because I have a memory tool telling me the parts of that signaling cascade. So if I can start there, I can start labeling things and then I'll be able to see the parts that are different right away, and that's part of what we have to do here anyway. So remember our memory tool for that was holding really great activities at camp kinase. So holding really great activities at camp kinase. Alright, So now let's see what matches up here on this list. Well, that H was for the hormone, and we're always going to start with a hormone. And so in our image here, we see that hormone right there, and the hormone is letter e. So I'm going to cross that out and I'm going to write e next to the hormone. The hormone is going to bind to the receptor, and that's what the receptor that stands for. The receptor, in this case, a G protein-coupled receptor. As we look down, f is the receptor, so that's receptor and here's our receptor right here. So, I'm going to label this one f. Now the receptor, this G protein-coupled receptor, activates a G protein. And I see on my image, here's this molecule in green that we have as a G protein being activated by that G protein-coupled receptor. So I look here, that's B. So I'm going to cross this out and put B on the line next to my G protein. Now remember that G protein is going to diffuse across the membrane and it's going to bind to this pink molecule here, this is an enzyme. In our cyclic AMP signaling cascade, that was our adenylate cyclase. But there's no adenylate cyclase on this list because remember we said one of the key differences here this is where it starts to really change is that this is going to use a different enzyme. It's going to use the enzyme phospholipase C. So this pink molecule here, I'm pretty sure, is phospholipase C. So I'm going to cross that out and I'll put an A on the line there. And that enzyme is then going to catalyze a reaction and it's going to produce the secondary So we're producing the molecules IP3 and DAG. But that's what we produce. Remember, we make those molecules from splitting another molecule. Molecule. The molecule we split is going to be that PIP2, or PIP2 molecule labeled here C. So I'm going to cross that out, and that has to be right here. We see here this molecule that's up against the enzyme, and you can see 2 arrows coming out of it because it's getting split into those 2-second messengers. Now PIP2 here, it's actually a molecule that's embedded in the membrane, so it's sort of stuck up on the membrane. And that's why you see it drawn like that there. Now it gets split into our 2 second messagers: our IP3 and our DAG, and we see 2 things coming out of here. And on this list here, we have just one letter, DAG and IP3. So these two things here, those are our 2nd messengers. I'm going to label them both as G. We'll figure out which is which in just a second, so I can cross that out. And then remember the 2 things that they go off and do. Well, that IP3 or we'll start with the DAG. Remember, the DAG goes off and it activates a kinase. Specifically, it activates protein kinase C. So when I look here, this here looks more like, an enzyme that could something that could be an enzyme, a kinase, that molecule there. So I'm pretty sure that that's going to be my option D, my kinase. So I'm going to put D on the line there, and I'll cross out kinase. And then, our IP3, remember it goes off and it causes the release of calcium ions into the cell. And while they're not to scale, this sort of looks like what I might imagine how you draw calcium ions. And so here we have our calcium ions, and calcium ions here are H. So I'm going to cross out that and put an H here. Now that means while we labeled both of these G, this one must actually be the IP3 and this molecule up here is actually the DAG. Alright. So we've labeled our diagram. Now we want to go through and try and figure out how is this different from our cyclic AMP cascade. Which parts are the same and which parts are different? Now to be really technical, all the parts except for the hormone are going to be different. It's going to use a different G protein-coupled receptor. It's going to use a different G protein, etcetera, and so on. But some of these things we've just sort of labeled generally, and so we want to think about the things where we're specific enough to actually call them different things. We want to call those out, and then we want to sort of see which things generally work the same way. So we started out with a hormone. Again, it might be the exact same hormone, so that's the same. And then next, we bind to a GPCR. Now both signaling cascades use a GPCR. The GPCR activates a G protein. Both signaling cascades activate a G protein. The G protein diffuses across the membrane and it binds to an enzyme. Both use an enzyme, but here we've been specific in the name and we're using a different enzyme. In the cyclic AMP cascade, we use adenylate cyclase. Here, we are using phospholipase C. So I'm going to circle this enzyme here. We've called this something different. Alright, now this enzyme is going to produce a second messenger, but again we've been specific in the molecules here, so I think we can call these things out as different. Cyclic AMP, remember, converts ATP into cyclic AMP. But here we have the molecule right here. I'm going to circle the molecule PIP2 being converted into DAG, which is not found in our other cascade, and into IP3, which is in our other cascade. Now IP3 goes on to cause the release of calcium ions in the cell, and that's not something that we talked about as a direct result of that cyclic AMP signaling cascade, so I'm also going to circle the calcium ions. DAG goes on to activate a protein kinase. Now we've said this is a different protein kinase. It's protein kinase C versus protein kinase A that's used in the cyclic AMP cascade. However, here we have only labeled it as a kinase. We haven't gotten more specific here, so I'm not going to circle this one. In both cases, that molecule ends up being activated as a kinase. Alright. So that's what I see when we get to this level of specificity is different. And generally, just to step back one more time, remember this is how the same hormone can cause multiple different cellular responses in different cells because the secondary messengers used are going to be different. Alright. Practice problems after this. I'll see you there.

You are studying how a hormone affects a cell and find that when oxytocin binds the receptor, the intracellular $Ca$$^2$$^+$ concentration increases. Based on this information, what could you logically conclude about this cell and hormone?

• A. The cell uses adenylate cyclase as a second messenger.
• B. Oxytocin directly interacts with the DNA of the cell.
• C. The cell uses $IP_3$ and DAG as secondary messengers.
• D. Both A & B are correct.

cAMP, $IP_3$, and DAG are all molecules that are used as secondary messengers. Which statement below correctly identifies a difference between the pathways in which they are found?

• A. cAMP secondary messenger systems result in the activation of a kinase, while systems that use $IP_3$ and DAG do not.
• B. cAMP and $IP_3$ are part of the same signaling cascade, while DAG is found in different cascades.
• C. Adenylate cyclase produces cAMP while phospholipase C produces $IP_3$ and DAG.
• D. Both A & C are correct.

Here’s what students ask on this topic:

What are G protein-coupled receptors (GPCRs) and how do they function in hormone signaling?

G protein-coupled receptors (GPCRs) are a large class of membrane-bound receptors that play a crucial role in hormone signaling. When a hormone binds to a GPCR on the cell surface, it activates the receptor, which in turn activates an associated G protein by replacing GDP with GTP. The activated G protein then diffuses along the membrane to activate other enzymes, such as adenylate cyclase. This enzyme converts ATP to cyclic AMP (cAMP), a secondary messenger that amplifies the signal and activates protein kinases, leading to various cellular responses. GPCRs are involved in many physiological processes, including vision, smell, and neurotransmission.

How does the cyclic AMP (cAMP) signaling cascade work?

The cyclic AMP (cAMP) signaling cascade begins when a hormone binds to a GPCR on the cell membrane. This activates a G protein, which then activates adenylate cyclase. Adenylate cyclase converts ATP to cAMP, a secondary messenger. cAMP activates protein kinase A (PKA), which phosphorylates various proteins in the cell, leading to a cellular response. This cascade amplifies the initial signal, allowing a small amount of hormone to produce a significant physiological effect. The process involves multiple steps, each amplifying the signal, resulting in a robust cellular response.

What is signal amplification in the context of secondary messenger systems?

Signal amplification in secondary messenger systems refers to the process where a single hormone-receptor interaction leads to the activation of multiple downstream molecules, significantly increasing the overall signal. For example, in the cAMP pathway, one activated GPCR can activate multiple G proteins, each of which can activate adenylate cyclase to produce many cAMP molecules. These cAMP molecules then activate multiple protein kinase A (PKA) enzymes, which phosphorylate numerous target proteins. This amplification ensures that even a small amount of hormone can trigger a large cellular response.

How do different target cells respond differently to the same hormone?

Different target cells respond differently to the same hormone due to variations in their receptors and secondary messengers. A hormone can bind to different GPCRs on different cells, initiating distinct signaling cascades. For instance, epinephrine can bind to beta-2 receptors in bronchial smooth muscle, leading to cAMP production and vasodilation, while binding to alpha-1 receptors in arterial smooth muscle triggers the IP3/DAG pathway, causing vasoconstriction. Additionally, the presence of different kinases and proteins in various cells further diversifies the cellular responses, allowing the same hormone to have multiple physiological effects.

What roles do DAG and IP3 play in secondary messenger systems?

DAG (diacylglycerol) and IP3 (inositol trisphosphate) are secondary messengers involved in a signaling pathway distinct from the cAMP pathway. When a hormone binds to a specific GPCR, it activates a G protein, which then activates the enzyme phospholipase C. Phospholipase C cleaves PIP2 into DAG and IP3. DAG remains in the membrane and activates protein kinase C (PKC), which phosphorylates various proteins. IP3 diffuses into the cytoplasm and triggers the release of calcium ions from intracellular stores, further activating other proteins and enzymes. Together, DAG and IP3 mediate diverse cellular responses.