Signal Transduction Pathways

Hi. It’s Mr. Andersen and welcome to Biology Essentials video number 38. This is on Signal Transduction Pathways. Signal transduction pathways are very important in the action of cells but they’re sometimes misunderstood. So I wanted to start with a analogy. And so when Jimi Hendrix plays the guitar he would vibrate the strings on the guitar. Those would then be transduced, in other words the pick up in the guitar, the electric pick up in the guitar has magnets and wires inside it and what it does is it transduces that message of the wires into an electrical signal. It then goes into an amplifier where you can make it really, really loud and so we can hear it. And that’s what he was famous for. And so signal transduction pathways in cells do the same thing. It starts with a message and that message is in the form of a chemical message and then that’s transduced into actions within the cell. And it also can be amplified. And so signal transduction pathways all work in the same way. And there are a couple of ways that their actions work Sometimes they will actually modify a protein or change the shape or the confirmation of a protein. But mostly what they’ll do, is there will be what’s called a phosphorylation cascade. In other words a phosphate group, which remember carries energy will be passed off from one chemical to another to another to another until it eventually has an action. And protein kinases are important in that. And so the example that I am going to give you today a message comes in. A message is picked up by receptors, and so this line we can say is the cell membrane on the outside of the cell. That message will dock with the receptor, and when it does that, in this case it will change the shape of that receptor. The example I’ll give you is called the G-Protein receptor Then we’ll have transduction. Transduction remember is when we’re switching that message and we’re changing that from a signal message on the outside of a cell to a message within the cell. We use what are called secondary messengers. The one that I’ll give you an example of is called cyclic AMP (cAMP). It’s a very common messenger in cells. And then that will eventually target the cells. In this case it’s going to target cells in the liver and it’s going to make them release glucose from glycogen. And so that’s kind of a signal transduction pathway. It starts with a message and then it eventually has some kind of a target within the cell. And so let’s get started. This is an animation of this typical liver cell and how epinephrine can effect it. And so we’re going to go through and I’ll pause at a couple of different spots and explain it. So epinephrine is the messenger Epinephrine is going to be given off from the adrenal gland. It’s going to move throughout your body. But it’s going to especially effect cells in the liver. So epinephrine is going to dock with this receptor. In this case it’s called a G-protein receptor. And so the epinephrine is what’s called a ligand. And so a ligand is going to be a chemical. It’s a chemical that can’t make its way through this cell membrane. It can’t make it through this hydrophobic region so it’s going to dock with the G-protein on the outside. G-protein is a protein that’s embedded within. It’s actually, it’s a snaky looking kind of a protein. It’s embedded within that cell membrane. So it’s got a portion on the top and it’s got a portion on the bottom It’s got these units on the bottom, they’re called subunits. And so what happens is when that ligand attaches, in this case epinephrine, with the G-protein it causes a conformational change in that protein. So it’s changing the shape of the protein. What happens when it changes that shape is it actually releases one of those alpha subunits. And so one of the subunits, called the alpha subunit will be released and it’s going to move to a protein just right down the way in the cell membrane This protein is called adenylyl cyclase and it’ll make sense why it’s called cyclase in just a second. But essentially what it is is before the actual alpha subunit comes, it’s an inactivated enzyme. In other words it’s an enzyme that’s not working yet. It hasn’t changed its shape so it’s actually a functioning enzyme. But once the alpha subunit is in place, it’s ready to do it’s job as an enzyme. And in this case what it does is it converts ATP, adenosine triphosphate into cAMP, or we sometimes call this “camp”. Now what is ATP? You remember, we know that that has three phosphates attached on the outside. It carries energy mostly in cells. We’re very familiar with how ATP can be converted to ADP when it drops off one of those phosphates, but it can also drop off two phosphates and that’s what happens in this case. So now it becomes AMP or monophosphate But there’s also a cyclic portion to it. And so it adds, right where we come off of the sugar it’s actually going to make a cyclic portion, I’ll put a picture in here, of that molecule ATP and now we’ve created these messengers Messengers are going to spread throughout the cell and this is called cyclic AMP. And

those secondary messengers in this case are going to target something called the protein kinase. Protein kinase, it’s made up of a number of different subunits of protein. But kinase means it does something or it does action In this case this protein kinase is going to have two catalytic subunits. Catalytic means things that are going to speed or speed up chemical reactions. And then it has these two regulatory subunits. And so once, as long as the regulatory portions are attached to the catalytic portions, proteins kinase is inactivated. It’s not going to do anything But let’s watch what happens to the cAMP It’ll actually bind to those regulatory portions of the protein kinase and it releases the catalytic portions. And so now we have this cascade. In other words we have this cascade of energy. Those catalytic portions are going to become phosphorylated. In other words they’re going to pick up energy from ATP and they’re going to become activated and they change from kind of a green to kind of a yellow activated color. They then can act on enzymes within the cell. Sometimes they’ll act through a number of different cells, number of different excuse me, molecules within the cell. In this case it’s going to drop off that phosphate to phosphorylase and it’s going to activate phosphorylase so it can release glucose from glycogen within the cell. Now once we don’t have that ligand attached anymore, we don’t make that cAMP, then the whole thing is going to shut down again. And so the signal transduction pathway is simply a way that we can take this message and we can move it throughout the cell and then have desired consequences within the cell. Okay, so let’s do a little review and if you’ve ever watched the show Dora the Explorer there’ll be times where she just kind of pauses and looks awkwardly at the person who’s watching the show and so that’s where you’ve got to jump in and help a little bit. So let’s do a little bit of review. So we start with this at the top. We’ve got epinephrine at the top. And so what do we call this . . That’s right. It’s called a ligand. A ligand is a chemical that can’t make entry into the cell, but it’s going to attach to the receptor So this is called the receptor. Do you remember what that’s called . . . That’s right. It’s called the G-protein. And so what’ll happen is that ligand will attach to the G-protein It’s got a number of different subunits. This one right here on the end is called the . . . alpha subunit, that’s right. Hey, if you’re not getting any of these you may want to go back and watch the earlier portions of the video We’ve got this over here, and this is probably the one that you’re going to struggle with the most. What’s the name of that . . . That’s right. Adenylyl cyclase. And so what happens is the alpha subunit is going to attach to adenylyl cyclase. We then have an enzyme that’s functioning. It’s going to take in these little starbursts. Those aren’t starbursts, they’re called . . . that’s right ATP. ATP will then be converted to . . . cyclic AMP or cAMP and cAMP are now going to go work on this . . . protein kinase. That’s right. Protein kinase. It has two portions that are . . . catalytic and two that are . . . regulatory. That’s right Okay, so the cAMP is going to move over to that. But let’s watch what happens for a second Because there’s not just a few cAMPs in the cell. There are going to be lots of cAMPs and lots of protein kinases in the cell. And so remember when we talked about our analogy of Jimi Hendrix, this is where we can amplify the message. So we just have this one ligand up here but we can have all this action going on. I didn’t want to animate all of that so I went back to just one protein kinase. So we will free up the catalytic portions. We now add energy to them. What’s that called . . Phosphorylation. That’s right. We’re going to add a phosphate group to them, they’re going to turn yellow and now they’re able to pass on that phosphate group to phosphorylase So it’s activated and it can break down glycogen into glucose within the cell. And so that’s the signal transduction pathway. It’s fairly simple. It’s got a lot of steps in it, but it’s just like playing the electric guitar And so I hope that’s helpful