Enzyme Linked Receptors

Voiceover: In this video we're gonna learn about enzyme-linked receptors. Like all cell membrane receptors enzyme-linked receptors receives signal from the environment and they instruct the cell to do certain things. Like most, enzyme-linked receptors are transmembrane proteins but they are unique because in addition to receiving signals from chemical messengers they also function as enzymes. Binding of a signaling molecule activates the receptor's enzymatic activity. Enzymes are a substance in our body that act as a catalyst which can speed up particular biochemical reactions. Enzyme-linked receptors are also called catalytic receptors. Over here I've predrawn a picture of our cell membrane. This is our phospholipid by layer. Up top I'm gonna say this is our extra cellular environment and below is our intracellular environment. This is inside our cell where our cytosol and all of our organelles are located. Let's talk a little bit about the structure of enzyme-linked receptors. The general structure of enzyme-linked receptors are shaped like this. Up top here you can see there is a shape which can bind a ligand. This over here is our ligand-binding domain. This is our extracellular portion. Down here, this half of the protein on the intracellular side is our enzymatic domain. It's our functional domain. This is the part of the enzyme-linked receptor that can act as an enzyme. When we have a ligand up here and what it binds in. The extracellular side can bind a ligand which will cause the intracellular side to act as an enzyme. Though there are many different types of enzyme-linked receptors, the most widely recognized and most common enzyme-linked receptors are called receptor tyrosine kinases. They're particularly important because they regulate cell growth, differentiation and survival. They can bind and respond to ligands such as growth factors. These are also called RTKs for short. The structure and function of RTKs aren't really a mystery. It really is writing the name. Part of the reason why receptor tyrosine kinases are unique is because they have tyrosine. If you go ahead and draw out a receptor like this. They're unique because tyrosine is on the intracellular enzymatic section. We can have tyrosine like this. Now that we've addressed the tyrosine portion of the name what do you suppose a kinase means? A kinase is a general term for something that has the ability to transfer phosphorus molecules. Usually from a high energy substance like ATP. Receptor tyrosine kinases have the ability to transfer phosphorus from ATP to intracellular proteins which activates them. That's the enzymatic function of receptor tyrosine kinases to transfer these phosphorus molecules. These proteins which are now phosphorylated can carry out a message through signal transduction. Now let's talk a little bit in more detail about this particular process. We'll talk about why in a second but receptor tyrosine kinases occur in pairs. If you can find one receptor tyrosine kinase you'll find another one that's fairly nearby. Down here we have our tyrosine. Out here we have our extracellular signal. Now let's say that this signal is now binding into that ligand-binding site. What's unique about receptor tyrosine kinase is that these two pairs are gonna come together and act together. Let's go ahead and draw these two pairs close together like this. At this point, our ligand is bound. We have our tyrosine on the bottom here. When this signaling molecule binds to an RTK they cause neighboring RTKs to associate with each other forming what we call a cross-linked dimer. This new thing that's formed when these two come together is a cross-linked dimer. RTKs need to act in pairs. Now the reason why is because cross-linking activates the tyrosine kinase activity in these RTKs through phosphorylation. Now these tyrosine are active and they can start getting phosphorus's. Each RTK in the dimer phosphorylates the tyrosines on the other RTK. There aren't always two tyrosines. There usually are multiple ones. For the sake of clarity I've only drawn in two though. This process of one phosphorylating the other is called cross-phosphorylation. If we have ATP inside the cell these tyrosines will cause it to become ADP with a phosphate group. This tyrosine molecule now that we have our cross-linked dimer is going to go ahead and pick up this free floating phosphate group. Now at a certain point each one of these, each one of the tyrosines are gonna get a phosphate group from ATP. Again, the reason why they need to act in pair is because one receptor tyrosine kinase will phosphorylate the other one. Once cross-phosphorylated, the intracellular cytoplasmic section so the enzymatic section of these RTKs serve as docking platforms for different intracellular proteins involved in signal transduction. Once we have these phosphorus's on the tyrosine different proteins can come by and attach themselves to them. For example, we could have one type of protein and we could also have another type of protein. They don't have to be the same one. Now the only thing that these proteins really need to have to dock with the phosphorus is a special domain specifically called SH2. This can bind to these phosphorylated tyrosines. Again, multiple different SH2-containing proteins can bind at the same time to any of these phosphorus. We've only drawn proteins on this one side but the same or different proteins can also bind on the other side. This allows activation of multiple different intracellular signaling pathways at the same time. Now after that, the signaling process can be really complex and often they can even end at the nucleus which affects gene transcription. Here, now that we have our proteins bound we're gonna have our signal transduction so the signal's gonna passed on into to the cytosol and ultimately this often ends in regulating gene transcription. Which ultimately affects the production of proteins. What do RTKs actually do in our body? Enzyme-linked receptors in general have a variety of functions but receptor tyrosine kinase is again one of the most famous and most well-known enzyme-linked receptors, and these are primarily known for their role in growth factors. Such as in regulating surface proteins called ephrins which can help guide developmental processes involved in tissue architecture, placement of nerve endings and blood vessel maturation. Other growth factors including things like nerve growth factors and platelet-derived growth factors also use RTKs. Another thing that RTKs are famous for is they can also bind hormones most famously insulin. Now what happens when RTKs fail to function properly? Since RTKs primarily regulate cell growth they can cause issues in the growth and differentiation of cells if they're not working. In fact, because of this many cancers involve mutations in RTKs. For this reason, RTKs are actually a target of many drugs that are used in chemotherapy. For example, the breast cancer drugs Herceptin is an antibody that binds and inhibits a particular RTK that is over expressed in many different breast cancers. In summary, enzyme-linked receptors essentially turn an extracellular chemical signal into enzyme activity inside the cell. Specifically the most well-known of those are receptor tyrosine kinases. These are the largest and most well-known group. The binding of a signaling molecule with an RTK activates tyrosine kinase in the cytoplasmic section of the receptor. This activity then can lodge a series of many different enzymatic reactions, it can bind different proteins which ultimately undergo complicated signal transduction generally carrying the signal to the nucleus which can then alter gene expression.