Alright. So here we're going to revisit our map of the lesson on bio signaling pathways, which is down below right here. And of course, we know that we've been exploring this map by following the left most branches. And so we've already talked about G protein coupled receptors, or GPC are in terms of the dental it cyclist GPC are signaling pathway. Uh, the stimulatory pathway, including C and and P K, as well as the inhibitory pathway including drugs and toxins affecting GPC are signaling. And then we also talked about fossil onasa, Tiggy PCR signaling and all of these secondary messengers and enzymes down below. And so now that we've explored our G protein coupled receptors branch to its entirety, we're now going to zoom out and start to explore a brand new branch on receptor tire seeing kindnesses or rt case. And so we'll get to introduce these right now. So let's get started. Alright, so here we're going to introduce a different type of bio signaling receptor other than the GP CRS, and these are the receptor tyrosine, kindnesses, and so the receptor tyrosine kindnesses, as you can see by these three bold ID letters here are commonly abbreviated as just are T. K's. And so, as you can see by their name, these receptor tyrosine kindnesses are indeed receptor proteins themselves on. So this is a receptor protein, which means that it's going to be an integral membrane protein but more specifically, the receptor tyrosine, kindnesses or RT. K s r receptors with an interest cellular Tyra seen kindness domain and so recall that the abbreviation the three letter abbreviation for the amino acid residue tyrosine is T. Y r. And so we already briefly introduced tyrosine kindnesses in our previous lesson videos and so recall that tire ASEAN kindnesses are kindness enzymes themselves. Which means that these air enzymes that air going to fuss for late as their name indicates tyrosine residues on specific target proteins. And we'll talk more about this idea right here as we move forward in our course Now notice down below, we're going to introduce the three domains that air found in receptor tyrosine, kindness or rtk monomers. And so notice that we have each of these three domains numbered right here and they're also color coded to these monomers that you see over over here and this part of our image. And so the very first domain is going to be an extra cellular like and binding domain. And so you can see that we have here. This green shaded region is representing this first domain, the extra cellular like and binding domain, and it does exactly what it sounds like. It's going to be on the extra cellular side or the outside of the plasma membrane, and it is going to bind to the ligand. And so you can see that the lie guns here are shown in blue and again, the extra cellular ligand binding domains of these arty case here are shown and green. And so, of course, the lie gone is going to bind to the ligand binding domain. Now, the next domain that we have here is a single trans membrane Alfa helix. And so what you'll see is here we have a single trans membrane alfa helix that is spanning the entire membrane, allowing this protein to be an integral membrane protein. And over here we have another one as well. And so this represents one monomer and this represents another monomer over here. Now, the third and final domain in these rtk monomers are interest cellular, tyrus ing kindness domains. And so down here in purple, what we're showing you are these tyrosine kinase domains. And so these, uh, this portion of the receptor actually acts as an enzyme. They act as tyrosine, kindnesses and so this is important to keep in mind as we move forward in our course. And so this year concludes our brief introduction to receptor tyrosine kindnesses, and will continue to learn Mawr and Mawr about these receptor tyrosine kindnesses as we move along in our course. So I'll see you guys in our next video.
Receptor Tyrosine Kinases
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all right, So in this video, we're going to begin to introduce some of the functionality of receptor tyrosine, kindnesses or RT. K s. And by functionality. What we really mean is how exactly they work or operate within a cell. And more specifically, we're going to introduce the Di Maria's ation and the auto phosphor relation of these arty case. Now it turns out that there are actually several different RTK classes that exist, and these RTK classes differ from each other in several different ways, including structurally. However, when you take a closer look at all of these RTK classes, they really do show that they can and usually exist as monomers or individual protein sub units. And again, this is how they usually exist because in some cases they do not exist. This monomers and they exist as Dime er's and we'll be able to see an example of our TKs that exists as diners later in our course. But again, all I want you to know here is that they usually exist as monomers. However, although they usually exist as monomers, all RTK classes are always going to form some kind of dime er when they are activated. And of course, the dime er means that these two monomers are going to come together to form a complex. And so notice down below that we have these four steps numbered one through four to show the diamond ization and auto phosphor relation of art case and notice that the numbers that we have up above in our text actually correspond with numbers that we have down below in our image. And so, in the very first step of the diamond ization and auto phosphor relation of rt case, what we have is just lie Gand binding, which pretty much is exactly what it sounds like. The lie Gand, which is again the extra cellular primary messenger. The Lagan molecule is going toe bind to the rtk. And so if we take a look at our image down below of our step number one over here on the far left. Notice what we're showing you is ligand binding and noticed that the lie again we're showing you as this diamond shaped blue molecule and notice that the receptor tyrosine kindnesses that we're showing you here are as, ah separate individual monomer. So we have one monomer circled in red over here and another monomer circled and red over here. And so these air separate individual arctic monomers. And each of them has their own extra cellular ligand binding domain here in green so they can each bind their own ligand. And so really, that is it for step number one that leads us to step number two and and step number two. What we have is Di Maria is a shin and so, essentially, what we're what we're going to see is that lie again. Binding to the RTK is going to cause a confirmation will change in the RTK and that confirmation will change is going to cause to rtk monomers to actually dime arise with each other and again by dime arise. What we mean is that they're going to come together and form a complex with each other. And this diamond ization step again is going to occur on Lee if it has not already dime arised and again later in our course, we're going to see an exception where the Arctic already exists as a dime er And so if it already exists as a dime er then you can pretty much think That's step number two here is just going to be skipped. And so, depending on if the Arctic is already dime arised or not, then the ligand binding and or the rtk di Maria's ation is going to lead to partial activation. It's going to partially activate both tyrosine kindness, domains on both receptor tyrosine, kindness, monomers. And so, if we take a look at our step number two down below notice that we're showing you the Di Maria's ation off the receptor tyrosine, kindnesses. And so notice that we're showing you here with these arrows the movement of these two rtk monomers together forming a dime er And so notice that upon Dima Riz ation that they're much closer together in forming a complex with each other now that it actually leads to partial activation off the receptor tyrosine kindness uh, kindness domains, which are these intracellular purple domains that you see down below? And what you'll notice is that within these, uh, domains that you'll see these wise here. And we're called that the why is the one letter amino acid code for tyrosine amino acid residues. And so you can see that we're just labeling some tyrosine amino acid residues here and these tires in kindness, domains and so after diamond ization is complete, and we have partial activation of the tyrosine kinase domains that leads us to step number three and in step number three. What we have is the auto phosphor relation of the RT case, and so auto phosphor relation is really just really just means self phosphor elation when a protein phosphor relates itself, or when a protein dime er's are phosphor relating each other, the monomers within the dimmer, our fast for relating each other. And so, in this step of auto phosphor relation, what we'll see is that the partially activated tyrosine kinase domains again, these partial, this partial activation is going to allow the tyrosine kinase domains to auto Foss for late each other or to cross phosphor relate each other. And so here we could also put the word cross phosphor late. And so we'll be able to see that down below in our image. And of course, this cross phosphor relation. This auto phosphor relation leads to the full activation of the tire seen kindness domains. And so if we take a look at our step number three down below notice that we're showing you the auto phosphor relation off these tyrosine kinase domains. And so notice that again partial activation in the previous step is going to allow these two domains too fast for early each other to cross phosphor early each other in a process known as auto phosphor relation. And they are tiresome kindness domain. So they fast for late. Specifically, that's higher. Seen residues on Thea opposite monitor. And again, the auto phosphor relation of these domains actually leads to the full activation of these tiresome kindness domains, and that leads us to our step number four. And so, in our final step, Step Number four, What we have is the RTK will phosphor lee its targets. And so the auto phosphor related RTK. Now that it is fully activated, it can now phosphor late other target proteins and so ultimately, this is going to lead to a cascade of phosphor elation. And the cascade of phosphor elation results in changes to metabolism and gene expression, which ultimately leads to the cell response that's associated with the bio signaling involving these receptor tyrosine kindnesses. And so if we take a look at our step number four down below. Over here. Notice that we're showing you the RTK target phosphor relation. And so now that we have a fully activated auto phosphor related to ever seen kindness domains, they can now phosphor late. Other target proteins such as this target protein here and phosphor relate them to alter their activity, and the alteration in their activity ultimately will lead to the cell response that's associated with RTK. Bio signaling. Now, as we move forward in our course, we'll be able to see more specific target proteins, and we'll be able to talk a lot Mawr about very specific receptor tyrosine, kindness, bio signaling pathways. But for now, this here concludes our introduction to the diamond ization and the auto phosphor relation of receptor, tyrosine, kindnesses and as we move forward in our course, will be able to get some practice applying some of these concepts. So I'll see you guys in our next video
Which of the following statements is NOT true of receptor tyrosine kinases?
Monomeric receptors are often induced to dimerize upon ligand binding.
The activated receptors attract and activate G proteins to continue the GPCR signaling pathway.
The cytoplasmic side of RTKs contains a kinase enzyme domain that is partially activated upon ligand binding.
Activated RTKs autophosphorylate themselves and can attract proteins with SH2 domains.
Receptor Tyrosine Kinases
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So in this video, we're going to introduce how some proteins with S H two domains are capable of binding to fuss for elated tyrosine residues which really makes these s h two domains super relevant to receptor tyrosine, kindnesses. And so here's what you guys need to know. Some proteins have what's known as a sark. Hm? Ology to domain. Or as you can see by the bold ID letters right here, an S H two domain for short. And so these particular proteins that have an S h two domain are capable of directly binding to fuss for elated tyrosine residues. Now, what's really important for you guys to note is that proteins that have these s H two domains do not bind to phosphor related Syrian or three Indian residues. Again, these proteins that have s h two domains can Onley bind to fox for elated tyrosine residues, which is again what makes these s H two domains so relevant to receptor tyrosine kindness is now the S H two domains of these proteins can either bind directly to number one auto phosphor related RT case or they combined directly to number two phosphor, elated target proteins of the RT case. And so notice that number one and number two here in the text corresponds with the number one and the number two that you see down below in our images. And so if we take a look at this image over here on the left hand side for number one, notice that we have a Ligon bound and dime arised and auto phosphor elated receptor tyrosine kindness here in the memory and notice that we also have this blue protein over here, and this blue protein noticed has an S H two domain. And again, the S H two domain allows it to bind fuss for related tyrosine residues. And again, why is the one letter amino acid code for tyrosine? And so you can see we have a phosphor related tire scene and the S H two domain is bound to that phosphor related tyrosine. And more specifically, the S H two domain of this blue protein right here is bound directly, uh, as we indicated up above, bound directly to the auto phosphor, elated receptor, tyrosine, kindness. And so notice down below. What we're saying is that in some cases, the S H two domains of some proteins will bind directly to the RTK or binds to our TKs directly. And so you can see that when the protein, the blue proteins s H two domain binds to the phosphor related tyrosine residue that can actually activate this protein. And this activated protein can ultimately generate the cell response that we're calling cell response number one here generically. But as we move forward in our course, we'll be able to see an example of this on MAWR detailed, but notice over here in the image on the right hand side again. Once again, we have our Ligon bound and dime arised and auto Foss for elated receptor, tyrosine, kindness or arctic. But this time noticed that the RTK is actually phosphor awaiting its target protein here. And because these are tyrosine kinase domains, we know that the target protein is fast for related at a tyrosine residue. And so notice that this yellow protein over here also has an S H two domain. Just like this protein over here has an S H two domain. But notice that this s H two domain over here on the yellow protein is not bound directly to the receptor tyrosine kindness like it was over here. Instead, this s H two domain of the yellow protein is bound to the phosphor related tire. Seen residue on the target protein off the rtk. As we indicated. Up above that, these S H two domains can bind directly to the phosphor related target proteins off the rt case. And so again, when the S H two domain of this protein binds to its phosphor related tyrosine residue, it can activate this protein and that activated protein can lead to the cell response that were calling cell response number two. And so this binding of the S H two domain can lead to a different cell response. Potentially then if the S H two domain binds directly to the phosphor related target protein and so that's important to keep in mind. And again, as we move forward in our course will be able to see examples of both of these scenarios on mawr detail on DSO noticed down below in our text here. What we're saying is that the S H two domains of some proteins are capable of binding not directly to the rtk, but instead buying directly to the phosphor related target protein. And so one thing that's also very important to note here is that proteins that have s H two domains can have a wide, wide variety of functions. And so because this protein with an S H two domain can have a different function, then this protein over here, which also has an S H two domain. This is what allows receptor tyrosine, kindnesses to elicit a wide variety of cell responses through their bio signaling. And so again, we'll be able to see examples of more specific rtk bio signaling pathways as we move forward in our course. But for now, this here concludes our introduction to how some proteins with S H two domains are capable of binding to phosphor related tyrosine residues. And so we'll be able to get some practice applying the concepts that we've learned as we move forward in our course. So I'll see you guys in our next video
Proteins that contain a src homology 2 domain (SH2 domain):
Have a phosphoserine residue that causes them to bind to other proteins.
Have a phosphotyrosine residue that causes them to bind to other proteins.
Bind to any proteins that have a phosphothreonine group.
Bind to proteins that have a phosphotyrosine residue and a specific conformation.