Alright. So here we're going to briefly 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 first and already at this point in our course we've covered the GPC are proteins, the G protein coupled receptors. And we've talked about all of these pathways that you see down below and our previous lesson videos. And so currently we've been exploring the new branch over here for receptor tyrosine, kindnesses. And so we're starting to make our way to talk about very specific receptor tyrosine kindnesses. So we've introduced insulin, and here in this video, we're going to introduce the insulin receptor. And so let's get started with that. So here we're going to introduce the insulin receptor as we introduce insulin, bio signaling, and so insulin signaling actually begins with just two steps that we have number down below number one and number two. And of course, the number one and number two in our text corresponds with the number one and the number two down below in our image. And so, in the very first step of insulin signaling. What we have is ligand binding, which is pretty much exactly what it sounds like the like and is going to bind to its receptor. Now we know that in insulin signaling the like and is going to be insulin itself, and we know that insulin can elicit a wide variety of biological effects. However, what's really important to note is that insulin actually does not enter cells. Instead, insulin is going to illicit all of its biological effects through bio signaling and signal trans duck shin. And so instead of entering cells, insulin is actually going to bind to an insulin receptor in the plasma membrane. And so the insulin receptor, as you can see by these bold letters right here is commonly abbreviated as just i n s are. And so the insulin receptor, or I N s r is really just a specific type of our T k or receptor tyrosine kindness. And it's going to be activated, of course, by insulin binding here, Which is why this step is called ligand binding. And of course, insulin is again going to be the lie gand here in this scenario. Now, the insulin receptor as we'll see down below in our image actually has four protein subunits. It has to Alfa sub units and two beta subunits that air linked together via di sulfide bonds. And you might recall that die sulfide bonds are co Vaillant bonds between the are groups of two Sistine residues. Now the insulin receptor is actually a little bit unusual because it's not like the other typical RT case that exist as individual separate monomers prior to like and binding. And so again, the reason the insulin receptor is so unusual is because even in the unlikely handed state, even when it's not bound to, it's like and insulin, the insulin receptor still already exists as to Alfa Beta dime er's. And so because it already exists as to Alfa Beta dimmers, really no diamond ization step is required because again, it's already existing as to Alfa Beta dime er's. And so if we take a look at our image down below, over here on the left hand side, notice at the top here. What we have is the insulin peptide, and so again, insulin is going to act as the like, and here, in this scenario and so notice. Below this, what we have is the insulin receptor that is again going to be embedded in the plasma membrane. And so notice that this insulin receptor has four protein subunits. It has to Alfa sub units that you see here and to trans membrane beta subunits. And so, of course, by the positioning here, you can see that the two Alfa sub units here in green are involved with ligand binding or binding to the insulin molecule. And of course, the two beta subunits are trans membrane and they contain the cytoplasmic tyrosine kindness, domains. Since again we know that the insulin receptor is an r t k a receptor, tyrosine Chinese and again. Another thing to note is that these, uh, sub units here on the insulin receptor are actually all die sulfide linked together. And so you can see those dice sulfide links here. And so what this means is that these guys are co violently linked together and they already exist, as we indicated above as to Alfa beta dime er. So here's one Alfa Beta dime er and here's the other Alfa Beta dime er and so again it already exists as a dime er, so we can pretty much skip the diamond ization step. And so, since we can skip the diamond ization step, of course, What that means is in step number two, what we have is the insulin receptor auto phosphor relation, which recall that auto phosphor relation is self phosphor relation or cross phosphor relation went to sub units, phosphor relate each other. And so this is when the tyrosine kinase domains in the insulin receptors beta sub units are going to cross phosphor early each other and thus activate each other. And so if we take a look down below notice in our step number two, what we have is the auto phosphor relation of the beta subunits of these, uh, of this insulin receptor. And so you can see here by these arrows that they're across phosphor relating each other at tyrosine residues. Recall that the wise are with one letter amino acid codes for tyrosine. And so what we have is the tyrosine residues being fussed for related, and that is going to fully activate the tyrosine kinase domains. And so here. What we're mentioning is that the Alfa and the beta domains are linked together via di sulfide bonds. And again, you can see those die sulfide bonds throughout our images right here. And so again, that means that we can skip the diamond ization step because it is already dime arised. And so that's why we have step number one like and binding and step number two auto phosphor relation. And so really again, This is the first two steps of insulin signaling and really, we've introduced our insulin receptor. And so that concludes this video, and I'll see you guys in our next one.
Insulin Receptor Example 1
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All right. So here we have an example problem that wants us to complete the sentence using one of these five potential answer options down below. And it says for the insulin receptor two transducers, the signal inside the cell and option A says the G Alfa sub unit needs to bind GTP toe, activate a dental it cyclists. Now, of course, what we need to recall from our previous lesson videos is that the insulin receptor is an R t k or a receptor tyrosine, kindness and receptor tyrosine kindnesses are different receptor proteins than G p, C, R s G protein coupled receptors, and so recall that G Alfa Sub unit is the sub unit of a G. Protein and G proteins are part of GP CR pathways, and they're not part of rtk pathways. And so what this means is that any of these answer options such as Option A and B that include G Alfa sub unit, is going to be incorrect because it's referring to the wrong type of pathway Now. Also, if we take a look at Option D, it says that it needs to recruit a tyrosine kindness, and so by recruitment, what that means is that it needs to essentially bring in a separate tyrosine kindness. But that is not what our T. K s need to do. RTK is already have a co violently bound tires and Chinese domain, and so really, they don't need to recruit tires. And kindness is for the most part, however, later in our course we will talk about an exception to this, uh, but here, the insulin receptor that we discussed in our last lesson video does not need to recruit a tiresome Chinese. Also, it does mention after demoralization. But again, we know that the insulin receptor is a unique rtk and the fact that it is actually already dime arised. And so there's really no diamond ization step that's required since it forms these Covalin die sulfide bonds between its Alfa Beta subunits. And so we can eliminate Option D. For those reasons and option, he says, it needs to recruit a tyrosine phosphate tastes toe phosphors late, the cytoplasmic dominating after demonization. And so again it's mentioning the recruitment, so we know that it doesn't actually need to recruit that, But also it says tyrosine, phosphate tastes and recall foster taste is do not fuss for late things. Instead, they do the opposite. They remove phosphate groups. And so for that reason, we know for sure this does not match up with the insulin receptor. And so, of course, this Onley leaves answer Option C as the correct answer. And so, for the insulin receptor to transducer the signal inside the cell it needs to activate. It's tiresome Chinese domains via auto phosphor relation after binding the insulin ligand. And so see here is the correct answer to this practice, and that concludes his practice or this example, and I'll see you guys in our next video.
The insulin receptor is an example of a _______:
G-protein coupled receptor.
Receptor tyrosine kinase.
Receptor tyrosine phosphatase.
Membrane channel protein.
Receptor threonine kinase.
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So in this video, we're going to introduce the insulin receptor substrates or I R s for short. And so again, the insulin receptor substrates. As you can see by these bold ID letter here's are commonly referred to as just I. R s insulin receptor substrates. And as their name implies, these air literally the sub streets of the fully active insulin receptor. And so more specifically, the insulin receptor substrates are actually really small proteins or peptides that again are going to be the main targets. And the main substrates of fully active auto phosphor related insulin receptor or I N s are Now, really there are many different types of insulin receptors, substrates or I R s that are distinguished from each other by numbers. And so I rs one is just one specific type of insulin receptors, substrate, but really moving forward in our course, Iris one is going to be the main, um, insulin receptor substrate that we're going to focus on in this clutch prep biochemistry course. And so again, I rs one is an insulin receptor substrate, and more specifically, I R s one is a secondary messenger that helps to transmit the insulin receptor signal as what's known as an adapter protein. But what in the world are thes adaptor proteins? Well, adaptor proteins are defined as proteins that lack enzymatic activity so they don't They don't actually catalyze any reaction. Instead, they serve mainly as a bridge to help bring other proteins together and to help continue the signal trans duck shin pathway. And so, if we take a look at our image down below notice over here on the left hand side, what we have is our Ligon bound are insulin bound insulin receptor here that is fully auto phosphor related and fully active. And so, of course, the fully active auto phosphor related insulin receptor that we have highlighted here. Eyes is going to have fully active tyrosine kinase domains that are capable of phosphor relating its targets or its substrates. And so here we're showing you the insulin receptor substrate one or I. R. S one and notice on the left. Here it is not phosphor related, but after the activity of the fully activated auto fuss related insulin receptor, notice that IRS one becomes phosphor elated at these positions here, and that activates I. R s one And so, because again, these are tyrosine kinase domains. That means that Iris one is going to be fast for related at tyrosine residues. Now, depending on the cell type and the conditions within the cell, I rs one can actually induce various other signaling pathways. And so what? We'll see moving forward in our course is that insolence? RtK signaling pathway is usually always going to result in i. R s one activation, as you can see down below the activated or fast food related I. R s one. But then after I r s one is activated, this actually is going to branch at this point. And so after again, I rs one activation it, then branches at this point. And so this is a very important thing for you guys to take note off. And so what this means is that I, R s one is going to act as a branch point in the insulin rtk signaling pathway. And so notice down below in our image right here. As soon as insulin binds and causes the auto phosphor relation of the insulin receptor and the insulin receptor phosphor relates and activates iris one again IRS one is going to act as a branch point, which is why we see that the signal transaction pathway splits a soon as iris one is activated. And so what you'll notice is that I RS one is going to act as an adaptor protein again, meaning that it does not have enzymatic activity. But it is going to bring other proteins together. And so, of course, it's the S H two domains of these proteins that will bind to the fuss for related tyrosine residues and so notice that it's capable of bringing together different proteins. And that, again, is part of what leads to this branch point. And so again, depending on the cell type in the conditions and the proteins that it brings together, um, this pathway could lead to a different cell response. So notice protein one here is leading to cell response number one, which would be, for example, changing glucose metabolism. But notice that bringing protein number two together with iris one would actually create a different cell response cell response number two, which could be, for instance, cell growth on regulation of gene expression and things like that. And so this is why we've seen that insulin can actually create several different biological effects. Partially because again, I rs one acts as this branch point now moving forward and our biochemistry course here. A clutch prep. We're going to talk specifically about the insulin rtk, signaling pathways that lead to sell response number one changes in glucose metabolism as well as the bio signaling pathways that lead to sell response number two cell growth. And so, first, we're going to start off with cell response number one glucose metabolism. So, uh, stay tuned as we move forward in our course and continue to talk. Maura, Maura about insulin and the insulin signaling So that concludes this video on the insulin receptor substrates or I R s and I'll see you guys in our next video.
Insulin binds to a receptor that:
I. Is coupled to a G protein. II. Possesses tyrosine kinase activity. III. Possesses serine/threonine phosphatase activity. IV. Interacts with the adapter protein IRS-1.
I, III and V.
II and IV.
I, II and V.
II, IV and V.
IV and V.
Which of the following is TRUE concerning the interaction between the insulin receptor and IRS-1:
The IRS protein phosphorylates the insulin receptor.
The β-subunits of the receptor bind to insulin, where each subunit has a separate insulin binding site.
Each β-subunit acts as a serine kinase and auto-phosphorylates the other subunit.
IRS is phosphorylated by the tyrosine kinase domains in the β-subunits of the insulin receptor.
IRS contains phosphorylated threonine residues that directly bind to insulin.