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Biochemistry

Learn the toughest concepts covered in Biochemistry with step-by-step video tutorials and practice problems by world-class tutors

12. Biosignaling

Insulin Signaling as a Growth Factor

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Insulin Signaling as a Growth Factor

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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 so already. In our previous lesson videos we've covered G protein coupled receptors or G p. C. R. S, as well as all of these specific GPC are signaling pathways down below. And so recently we've been exploring a new branch here for receptor, tyrosine, kindnesses or arty ks. And we've introduced insulin and the insulin receptor, which is an RTK. And we talked about a very specific insulin rtk signaling pathway on glucose metabolism which included the enzymes P three k, the substrate, pip three and the enzymes PKB, MPD K one. And so here in this video we're going to begin a new insulin rtk signaling pathway where insulin, instead of affecting glucose metabolism, is actually going to act as a growth factor. And so insulin rtk signaling as a growth factor, includes too many pathways that are embedded within this and these pathways are the wrasse pathway and the map k pathway. Now the wrasse pathway includes components, G R B two sauce and rass, of course, and the map K pathway includes the components Wrath one Mac and er cook and so moving forward in our course, we're going to discuss again the insulin RtK signaling pathway as a growth factor. And then we'll start with the wrasse pathway, which includes these components, and then later we'll follow up with the mat k pathway. And so let's go ahead and get started talking about this. All right, so here we're going to begin our introduction to insulin signaling as a growth factor and so recall that in our previous lesson videos, when we introduced insulin, we said that one of insolence primary biological effects was to decrease blood glucose concentration by regulating glucose metabolism, but also recall that in our previous lesson videos, we said that in addition to regulating glucose metabolism, insulin would also stimulate cell growth by regulating gene expression, and so insulin can also act as a growth factor. Now, insulin growth factor RTK signaling is actually triggered by the following pathway that you see right here G R B two, followed by sauce, followed by wrasse, followed by the map k pathway. And so, in our next lesson video, we're going to introduce these exact components that you see here. And then later we'll talk, Maura, about the map k pathway. But for now, this here concludes our introduction, and I'll see you guys in our next lesson video where we talk about the wrasse pathway. So see you guys there.
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Insulin Signaling as a Growth Factor

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So here we're going to begin our lesson on insulin growth factors signaling via the wrasse pathway and will introduce what this wrasse pathway is here very shortly. Now, first, we need to recall from our previous lesson videos that insulin results in an active and phosphor elated insulin receptors. Substrate one or I. R. S one. And so, just as a reminder notice over here on the left hand side of our image, we're showing you the 51 amino acid peptide hormone insulin binding to the insulin receptor. And when insulin binds to the insulin receptor, it activates the auto phosphor relation off the beta domains. And so these beta domains are tyrosine kinase domains, and so they fast for late tyrosine residues on each other. And that fully activates the tyrosine kinase domains here so that it can foss for late its substrate insulin receptor substrate one or iris one which leads to again an active and phosphor elated I rs one protein. And so again, this is a reminder from our previous lesson videos. We already knew that insulin would lead to active virus one, and so this is again a recall from our previous lesson videos that insulin results inactive virus one. And really, this is exactly where we pick up with when we start the wrasse pathway. We start the rest pathway with an active IRS want. And even though we're starting the wrasse pathway with active virus one, we still can't forget the previous steps here of the RTK, the insulin binding the auto phosphor relation and, again, the phosphor relation of IRS and to Iris one. And so that's just a reminder again from our previous lesson. Videos now also recall from our previous lesson videos that active I rs one really acts as a branch point, uh, and insulin bio signaling, and so it can actually lead to many different pathways. And you might recall, in our previous lesson videos, we saw active Ire s one, an insulin signaling on glucose metabolism. And here we're going to see Active Iris one once again. But this time it's not going to be involved in glucose metabolism. It's going to be involved and growth factors signaling. And so again, I rs one connect as a branch point in insulin bio signaling and can lead to many different pathways, including this wrasse pathway that we're about to introduce here. And so what is this wrasse here that the wrasse pathway is referring to? Well, wrasse is actually a lipid linked mon America g protein. But wait a second. I thought you said that G proteins were involved with G p C. R s G protein coupled receptors, not with Artie K's like the insulin receptor that we have down below. Well, it turns out that the wrasse G protein is actually an exception to this. And so wrasse is a G protein that is not involved with GP CRS. Instead, it's involved with the insulin rtk, a receptor tyrosine kindness and so another differences in our previous lesson videos with the GPC ours, the G proteins were hetero. Try Merrick G proteins, meaning that they had three different sub units the Alfa Beta and gamma sub units. But notice that this G protein here in Rast is not a hetero try Merrick G protein. Instead, it's a mono merrick g protein, meaning that it only has one single sub units instead of three different sub units. And so this wrasse g protein monem Eric G protein exists in two forms, as you might expect It exists in a GDP bound form, which is the inactive form, and it also exists in a GTP bound form, which is the active form. And so this is important to keep in mind as we move along and talk more about this wrasse pathway. And so it really the wrasse pathway is a three step cascade of protein interactions. And these three steps really lead to the activation off this wrasse G protein during insulin, signaling as a growth factor. And so notice down below, we have each of the three steps in this cascade numbered and our texts. And of course, the numbers that you see here in our text correspond with numbers that you see down below in our image. And so, in the very first step of this wrasse pathway again, we're starting with active I rs one. And so we're starting right here at this portion of our image. And so the active Iris one is going to serve as a binding site as an adaptor protein for the S H two domain of the adaptor protein called G R b two. And so, if we take a look at our image down below notice that I. R s one over here is acting as an adaptor protein and the S H two domain of this protein right here, which is G R B two is binding to the phosphor related tyrosine residue on iris one. And this is going to activate g R B two, which is another adaptor protein. Azzawi indicated up above that G r p g r B two is an adaptor protein, and so this leads us to step number two. And that is that G R B twos. S H three domain, which is on the opposite side of the protein, is going to serve as a binding site for another protein called sauce at sauce. When it binds to G R B two, it's going to form an I. R s one g r b two sauce complex, since they're all binding toe one another. And so, if we take a look at our step number two down below notice that the S H two domain over here of GRB two is binding to I. R s one. However, on the opposite end, we have an S H three domain on GRB two that is binding to this other orange protein over here that we're calling sauce. And so now what we have is an iris one a G r B two and a sauce complex after step number two, as we indicated up above. So then that leads us to step number three. And what's important to note is that the bound sauce protein is actually a Guan Ing exchange factor, which you can see by these bold letters. Here is abbreviated as a G e f or a GEF protein, and so the sauce. Because it is a guanine exchange factor, it's going to allow for the guanine exchange in our G protein. And so it's going to catalyze the replacement of G D. P, the low energy inactive form with G T. P, the high energy active form on our Rassmann America G protein. And so notice down below in our image in step number three right here that we have this green protein right here, which is a monem Eric G protein called wrasse and wrasse, is in its inactive state right here, originally where it is bound to GDP. But when sauce is bound to G R B two and sauce becomes activated and sauce can then act as the guanine exchange factor that it is or the gift that it iss. And it's going to catalyze the replacement of GDP with GTP toe, activate, rest. And so you can see that we have GTP replacing GDP here in the wrasse protein. And of course, over here, what we have is the wrasse bound to GTP, which is the active form of our Rassmann America G protein. And so this active rass will actually regulate cell growth via activation of another uh, signaling pathway called the map que signaling cascade or the map K signaling pathway. And so notice that here we're showing how rast, the active form of rass, will activate another pathway called the map K signal cascade. And we'll talk about this map k signal cascade in our next lesson video. But for now, this year actually concludes the wrasse pathway. The wrasse pathway ends with an active wrasse g protein. Now what's also important to note here is that very similar pathways to the one that we just discussed up above where iris one activates grb two activating sauce activating wrasse. Very similar pathways can also be initiated by other signaling molecules other than insulin, so they can be initiated by other by a variety of other growth factors such as, for example, e g f or epidermal growth factor or P D G F or platelet derived growth factor. And so here we have these abbreviations for you. And so you may see in some of your textbooks that insulin does not act as the lie gone for this pathway. But instead, perhaps it is again epidermal growth factor or E g f. Or perhaps even PD GF platelet derived growth factor, which again can stimulate very similar pathways to the one that we discussed up above. But this year concludes our introduction to the insulin growth factors signaling via the wrasse pathway, and we'll be able to get some practice applying this as we move along and, of course later, will continue to talk about the map K signaling cascade as well. So I'll see you guys in our next video
3
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Insulin Signaling as a Growth Factor Example 1

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all right. So here we have an example problem that wants us to complete the sentence here, using one of these four potential answer options down below. And it says that G proteins such as wrasse are activated when and of course, what we need to recall from our previous lesson videos is that rest is a monem eric g. Protein. And it is an exception to other G proteins that are involved with G protein coupled receptors, or GP CRS, because wrasse is not involved with GPC ours. Instead, it's going to be involved in insulin rtk, signaling pathways as a growth hormone and so wrasse. Although it is found in these rtk pathways, um, it's actually going to keep that same feature of activation as the other G proteins. And so, of course, what that means is that the activated wrasse is going to be active when it's bound to the GTP molecule. And so we can say that when it's bound to GTP, that's when G proteins such as rats are active and so we can go ahead and indicate that be here is the correct answer. Now A is incorrect because it says, bound to G D. P. But this is the low energy inactive form. And when wrasse is bound to g d. P, it would be inactive, just as we might expect with our other G proteins as well. And then, of course, we did not talk about wrasse getting phosphor related at any point. And so those two answers are incorrect. And again, Option B here is the correct answer. So that concludes this practice, and I are this example, and I'll see you guys in our next video.
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Problem

In the insulin signaling pathway to activate the protein Ras, activated IRS-1 binds to ___________.

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Insulin Signaling as a Growth Factor

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So in our last lesson video, we said that the wrasse pathway ends with an activated monem Eric wrasse g protein that ends up activating another pathway called the map K signaling cascade. And so here in this video, we're going to introduce what Map K is. And so Map K is really just in abbreviation for Mycogen activated Protein Kindnesses, As you can see by the first letter of each of these words, gives us map Ket. And so, as you can see by the name, these are indeed kindnesses themselves. And so they are going to be enzymes that foss for late there substrates. But more specifically, these Mycogen activated protein kindnesses, or Map K's are enzymes that phosphor late there substrates and lead to cell growth. And so what can remind us that these Map K's lead to cell growth is the word Mycogen itself? And so my trojans are really just a specific type of growth factor that, specifically induced might oh sis and cell division leading to cell growth. Now, what's really important to note about these map cases that these map K enzymes can actually be regulated and phosphor. Elated by other map K enzymes. And so if we take a look at our example, image down below of Matt Kindness map kindnesses. We will be able to understand this regulation and phosphor relation by other map case. And so, let's say down below here in this green circle, this represents our Mycogen activated protein chi nese our map K. And let's say that this map K because it is a kindness, it's going to go on toe Foss for late other substrates. But if this map K is regulated by phosphor elation by another kindness, then this kindness right here in red would be referred to as a map que kindness. Because this is a kindness that Foss for lates, the enzyme map K and so more specifically, we could refer to this enzyme right here as a map. Que que? Because it is a kindness that phosphor leads map, Chinese or map K. And if this enzyme right here is phosphor related and regulated by phosphor relation by another kindness up here, then this would be referred to as the map que que kindness, because this is a kindness that regulates map K. K. And so then this protein up here could be referred to as the map, K K K. And so what you end up getting is the map. KKK regulates map KK and map KK regulates map K and map K goes on to fuss for late the downstream targets that leads to my toasts and cell division. And so, as we move forward in our course, we're going to see some specific examples of map, KKK's map case and Map K's as well. So keep this regulation here in mind. And so this year concludes our brief introduction to Map K's, and in our next lesson, video will be able to continue our lesson on the map K signaling cascades so I'll see you guys there.
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Insulin Signaling as a Growth Factor

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So here we're going to discuss how the wrasse pathway that we covered in our previous lesson videos activates the map K signaling pathway. And so again, recall from our previous lesson videos that the wrasse pathway results and an active GTP bound wrasse protein that initiates another four step map k signaling cascade. And so notice down below. We're showing you each of the four steps in the map k signaling cascade as a continuation of the three steps from the wrasse pathway that we covered in our previous lesson videos. And so if we take a look at our image down below, over here on the left hand side, notice that we're pretty much showing you the same image from our previous lesson Videos of the Wrasse pathway. And so notice that the first three steps here Step one, Step two and Step three are shaded in gray because again, these are the steps that we already covered in our previous lesson. Videos of the wrasse pathway And so really the new steps that we're introducing here in this video are steps four, 56 and seven, which are really the four steps of the map case, signaling cascade that we're introducing here in this video. And so, of course, these steps 456 and seven that you see here correspond with the steps the number of steps up above in our text. 456 and seven. And so the very first step of the map K signaling cascade which would correspond to step for here is the active wrasse. GTP from our wrasse pathway is going to directly activate a map KKK, which is a kindness that regulates Ah map KK via phosphor relation. And this map KKK here is actually going to be the protein called Wrath one. And so, if we take a look at our image down below at step number four again, notice that step number four is starting with the active wrasse GTP protein That was the end result of the wrasse pathway. And so notice that this wrasse, this active wrasse GTP protein, is associating itself with this other protein called Wrath One and Wrath. One is our math k k K. And so really, that is it for our step number four right here. And that leads us directly into step number five and so in step number five. The activated wrath one protein this map KKK Because it is a kindness. It's going too fast for late to Syrian residues on a map KK called Mac M E K. And this is going to activate Mac. And so if we take a look at our step number five down below and our image over here, uh, notice that wrath one. The map. KKK is regulating another map KK via phosphor relation. And this map KK is Mac. And so what we can do is label Mech as the map k k. And so notice that when Mac is not phosphor related, it is in its inactive state. But as soon as wrath one Foss for late smack on these two Syrian residues, as we see here, the two fast for relations the two phosphate groups, MEC becomes active. And again, mech is a kindness itself. And so this is going to lead us directly into step number six. And so in step number six, the active Mac, which is again this map KK is going to fuss for a late the c a Syrian and Tyra seen on a map k called IRQ. And this is going to activate the map K called IRQ. And so if we take a look at our step number six down below notice that here what we have is our map k called IRQ, and notice that when ERK is not phosphor elated, it is inactive. But upon being phosphor, elated by the mat KK Mac, uh, it becomes active, and again irk represents our map. Okay, so we can label this as our map. Uh, okay, right here. And so this leads us directly into step seven. And in step seven, as you can see in our text above the active irk protein is going to enter into the nucleus of the cell, and it's going to regulate the activity of transcription factors. And these transcription factors that it regulates are specifically related to sell growth. And so that is what leads to cell growth here in this insulin signaling pathway as a growth hormone. Now, of course, you guys have probably covered what transcription factors are in your previous biology courses. But here we're just reminding you that transcription factors are really just proteins that induced, as their name implies, the process of transcription which recall is when DNA is transcribed into RNA. And so, of course, transcription factors will induce transcription of very specific target genes. And these specific target genes again are going to be related to cell growth here in this pathway. Now, in terms of the specific transcription factors that are affected by ERC, it turns out that IRK will actually regulate many different types of transcription factors. And so the ERC transcription factor targets actually include the transcription factors called Al Kwan Surf, June Foss and Mick and probably much more than that as well. And so, in terms of the exact transcription factors that you guys are responsible for knowing in this pathway, uh, that's actually going to depend on your professors. And so notice over here. What we have is this little hand symbol to remind you guys that you guys should raise your hand in class and ask your professor exactly which transcription factors are you guys responsible for knowing in this pathway. But if we take a look at our step number seven down below in our image, notice that the activated IRQ protein, which is our map kr Matt kindness, uh, in step number seven, it's going to enter into the nucleus of the cell, which we have over here in this corner, and it's going to regulate the activity of transcription factors that are related to cell growth. And so we have transcription factor regulation here, and so really, this is showing the entire pathway the insulin rtk signaling pathway as a growth factor. And so ultimately what you see is that insulin binding can lead to transcription factor regulation off cell growth. And so again, the insulin rtk signaling pathway on as a growth factor includes the wrasse pathway which are steps 12 and three here, as well as the map K pathway which are steps and seven. And so this here concludes our video on the introduction to how the wrasse pathway activates the map case signaling pathway and as we move forward in our course will be able to apply the concepts that we've learned. So I'll see you guys in our next video
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Insulin Signaling as a Growth Factor Example 2

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All right. So here we have an example Problem that says all of the following are true and the wrasse and map K pathways, except for which one of these four potential answer options down below. And of course, because we're looking for the exception here, really, we're looking for the false answer option. And so option A here says that g r B to change his confirmation and bind to the next protein sauce in the signal transaction pathway. And so recall from our previous lesson videos where we called where we covered the wrasse pathway, that option A here is actually a true statement. And so after g r b to bind to I. R s one, it's going to activate it and change its confirmation so that it combined to the next protein sauce. And so this is a true statement. So it's not the false exception that we're looking for and we can eliminate. Answer, option A now answer option. B says sauce acts as a gap in the activation of the protein rast. But maybe you don't remember us mentioning anything about gap here. So let's skip this one for now, and we'll come back to it a little bit later. Let's check Option C. So she says, wrasse exchanges GDP for GTP and activates Ralf one, which is the first kindness in the map k pathway. And so again, if you recall from our previous lesson videos, where we covered the map K pathway, that this is actually a true statement and so wrasse we know is a Mon America G protein. And the way that it becomes activated is by exchanging it's low energy G d. P for its high energy GTP. And the first thing that rats does when it becomes activated is it activates another map cake called Ralf one. And this is the first kindness in the map K pathway. So this is a true statement, and we can eliminate answer Option C because it's not the false exception that we're looking for. And so moving onto Option D here, it says, the map K pathway regulates transcription factors that regulate specific genes. And you might recall that this is also a true statement, and the reason that it's true is because recall that the map K pathway ends with the activation of the map K called IRQ, and irked makes its way into the nucleus to regulate transcription factors that regulates specific genes. So again, we can eliminate answer Option D because it's not the false exception that we're looking for. And so that must mean that option be here is the false exception that we are looking for. But what is false about Option B? Didn't we say that sauce was used to activate the protein wrasse? Well, that part of this answer is actually true. Sauce is used to activate the protein rests. However, sauce does not act as a gap, and we have not yet talked about gaps yet here in our course. But we will in our next lesson video. But sauce actually does not act as a gap. Instead, it acts as a GEF, a guanine exchange factor. And so the gap part is really what makes answer Option B, the false answer option that we were looking for. And so because answer Option B is the false exception that we're looking for, we could go ahead and mark this as theater we were looking for, and that concludes this practice or this example problem. And I'll see you guys in our next video
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Insulin Signaling as a Growth Factor

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So here in this video we're going to discuss the termination of insulin signaling as a growth factor. Now, just like all of the other G proteins that we talked about in our previous lesson videos the Monem Eric G protein wrasse also possesses GTP ace activity. Now recall that the G. T. P s activity is really just referring to the ability of these G proteins to cleave or hydrolyzed the high energy and active GTP into the low energy and inactive G. D. P. And so really wrasse is g TPS activity is serving to terminate the signal and to help reset the pathway back to the inactive state. Now what's really important to note about wrasse is GTP Ace activity is that wrasse is G TPS activity is actually very, very slow, so slow that it's actually not going to occur at a reasonable rate on its own. However, wrasse is GTP. Ace activity can actually be sped up with the help from other proteins. And so these other proteins that help to speed up wrasse is GTP s activity are called G TPS activating proteins, or G a P for short or just gap proteins and so these g TPS activating proteins or gaps as their name implies air just proteins that are going to activate the G. T. P s activity of wrasse. And so they're going to increase the rate of rashes, GTP, hydraulics, ISS which, of course, we mentioned up above is going to thus inactivate wrasse. And so notice that this dotted box that we have up above in our text corresponds with the dotted box that we have down below. In our image which is showing wrasse is GTP ace activity and so notice Over here on the right, what we have is the active wrasse which is bound to the high energy and active GTP and notice that the arrow pointing to the left is showing the reaction that in activates wrasse where it's going to hide relies the high energy active GTP into the low energy and inactive G d. P. But again, rass is GTP s activity is really, really slow. So it can Onley really occur with the help of other proteins called gap proteins. And so here in this blank we can fill in the gap and right and gap for these gap proteins and so the gap proteins they're going to help accelerate. Rass is GTP ace activity, where it will again cleave off one of the phosphate groups and form the low energy inactive GDP. And of course, once wrasse is inactive, that's going to help again terminate the insulin signal as a growth factor. Now, what's also important to note is we've got all of these red arrows down below in our image. And all of these red arrows are really just referring to phosphate aces, which recall are enzymes that remove phosphate groups and thus will reverse the kindness activity in this pathway. And so we know that the insulin signaling as a growth factor includes, um, the activity of a lot of different kindnesses that Foss for late things and so phosphate taste is air going to be really important to remove all of those phosphate groups, reverse the kindness activity and helped to reset the pathway back to the beginning. And so if we take a look at our image down below, notice that we have all of these red arrows and the red arrows are showing the phosphate taste activity, which removes the phosphate groups from all of these proteins and changes them to their inactive state. So you can see Mac years being, uh um, the foster taste activities acting on Mech, which is removing its phosphate taste. It's phosphate groups on even I rs one phosphate groups can be removed by phosphate aces and even the phosphate groups on the, uh, the insulin receptor, uh, domain. The tiresome Chinese domains can be removed as well. And so essentially, the main take away here of this video is that the removal of phosphate groups by phosphate aces and by wrasse is G TPS activity here, when it cleaves GTP and to GDP are really going to help terminate the signal and helped reset the entire pathway. And so this year really concludes our lesson on the termination of insulin signaling as a growth factor. And as we move forward in our course, we'll be able to get some practice applying these concepts. So I'll see you guys in our next video
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Problem

The monomeric G-protein Ras is activated by _______________, while _______________ helps turn Ras off.

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Insulin Signaling as a Growth Factor

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so as you guys have probably noticed from our previous lesson videos. When it comes to insulin signaling as a growth factor, there's a lot for you guys to remember. And so, how in the world are you guys supposed to remember the most important components in the correct order when it comes to insulin rtk signaling as a growth factor? Well, that's exactly what this video is all about right here, and I'm going to share with you Guys are really creative and unique story that you'll Onley find here a clutch prep that's designed intentionally to help you guys remember the most important components and in the correct order for insulin rtk signaling as a growth factor. And so what you'll notice is over here on the right hand side, we have this image that shows you the most important components in the correct order for insulin rtk signaling as a growth factor and so notice the top part up here represents the wrasse pathway and notice that it ends with rasp. And then, of course, the bottom pathway down here represents the map k pathway. And so both the wrasse pathway and the map K pathway are involved in insulin rtk signaling as a growth factor. And so notice over here on the left hand side, we're showing you the seven steps to this story. And these seven steps that you see here correspond with the seven steps from our previous lesson videos for insulin rtk signaling as a growth factor. And also these seven steps also correspond with the seven numbers that we have down below and our image. And so that's important to keep in mind as we move forward. Now this story is not fully bulletproof. It's not a perfect story to help you memorize all of the different details again. It's on Lee designed to help you guys memorize the most important components in the correct order. So because this pathway starts off with activated i. R. S one, the first step of our story is that the i. R s, the Internal Revenue Service gives another tax refund, and again, that represents I rs one. So if we take a look at our image down below, noticed that step one again. Is this cash influx or this tax refund that the IRS is providing? And so that leads us to our second step. And that is that the cell decides to use that money that tax refund money toe by two orders of wings on grubhub. And so the two orders on grubhub represents G R B to the adaptor protein that binds toe iris one. And so, if we take a look at our image down below, notice that we've got the grubhub symbol here and specifically we've got these two orders of chicken wings. And so the grubhub times to hear two orders on grubhub represents G R B two, and this leads us to our third step. And in our third step, we have When that grubhub food actually arrives, the cell decides to add some sauce, some hot sauce to it, and that reminds us of the sauce guanine exchange factor. And so we take a look at our image down below. Notice that the cell is gonna add some hot sauce, too. The grubhub wings. And so, after the cell, add some hot sauce. Hey, starts eating the food, and all of a sudden the hot sauce starts toe, activate a rash. And the rash, of course, represents the monem Eric Rash G protein. And so notice down below in our image. Step number four. He's saying, I got a rash from eating those chicken wings there. And so in step number five, the cell decides to call Dr Raphael and Dr Rapper Rafael represents the map cake called Wrath One. And so, if you take a look down below, you can see that we've got Dr Rath here on the phone since the cells giving him a call on he's, uh, doc. That leads us to step six. And so Dr Rath says he's going to make and making something represents the mat KK mech. He's gonna make the irking pain go away. And the irking pain, uh, here represents the mat k irq. And so you can see down below that Dr Rath tells the cell that he's going to make the irking pain go away So you can see we've got this IRK pill here for step number seven. And, of course, the ERC pill is going to make its way into the nucleus. And so you can see the guy's mouth over here represents the nucleus. And so it's a really silly, really crazy story, but it can helpful. It can be really helpful for memorizing the most important components of this pathway in the correct order. And so, by practicing the story just a handful of times, you guys will get this down. No problem. And so this year concludes our lesson on how to remember the insulin RTK signaling as a growth factor, and we'll be able to get some practice in our next couple of videos, so I'll see you guys there.
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Problem

Place the insulin RTK signaling events in order from 1-7:

a) Ligand binding results in autophosphorylation of the receptor tyrosine kinase ______.

b) MAPKK (Mek) phosphorylates MAPK (Erk) ______.

c) Sos binds then activates Ras ______.

d) Receptor tyrosine kinase phosphorylate IRS-1, which binds the SH2 domain of Grb2 ______.

e) Ras activates MAPKKK (Raf-1) ______.

f) MAPK (Erk) activates transcription factors to regulate mRNA synthesis ______.

g) MAPKKK (Raf-1) phosphorylates MAPKK (Mek) _______.

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12
Problem

Ras is estimated to be responsible for 30% of human cancers. Most mutations in Ras prevent the protein from binding GTPase-activation proteins (GAPs). What is the effect of this mutation on the signal transduction?

13
Problem

Insulin is one of the hormones/growth factors that will activate the Ras and MAP kinase pathway. Concerning this system, all of the following are true EXCEPT

14
Problem

All of the following are true in the Ras and MAPK pathway EXCEPT:

15
Problem

Guanine Exchange Factors (GEFs) bind Ras-GDP and promote dissociation of bound GDP to be replaced by GTP. GTPase Activating Proteins (GAPs) bind Ras-GTP and stimulates GTPase activity of Ras. How is the downstream signal affected by the presence of GEFs and GAPs?

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