Insulin Signaling as a Growth Factor - Video Tutorials & Practice Problems
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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 biosignalling pathways, which is down below right here. And, of course, we know that we've been exploring this map by following the leftmost branches first. And so already in our previous lesson videos, we've covered g protein coupled receptors or GPCRs, as well as all of these specific GPCR signaling pathways down below. And so recently, we've been exploring a new branch here for receptor Tyrosine Kinases or RTKs, 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 I three k, the substrate PIP 3, and the enzymes p k b and p d 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 RAS pathway and the mapk pathway. Now the ras pathway includes components, g r b 2, sauce, and ras, of course. And the mapk pathway includes the components RAF1, MEK, and ERK. 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 RAS 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. Alright. 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 insulin's 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, grb 2, followed by SARS, followed by RAS, 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 more about the mapk 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 RAS pathway. So see you guys there.
2
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Insulin Signaling as a Growth Factor
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10m
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So here we're going to begin our lesson on Insulin Growth Factor Signaling via the RAS pathway, and we'll introduce what this RAS pathway is here very shortly. Now first, we need to recall from our previous lesson videos that insulin results in an active and phosphorylated Insulin Receptor Substrate 1 or IRS 1. 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 autophosphorylation of the beta domains. And so these beta domains are Tyrosine Kinase domains and so they phosphorylate Tyrosine residues on each other. And that fully activates the Tyrosine Kinase domains here so that it can phosphorylate its substrate, insulin receptor substrate 1 or IRS 1, which leads to again an active and phosphorylated IRS 1 protein. And so again, this is a reminder from our previous lesson videos. We already knew that insulin would lead to active IRS 1. And so this is again a recall from our previous lesson videos that insulin results in active IRS 1. And really this is exactly where we pick up with when we start the RAAS pathway. We start the RAAS pathway with an active IRS 1. And even though we're starting the RAAS pathway with active IRS 1, we still can't forget the previous steps here of the RTK, the insulin binding, the autophosphorylation, and again the phosphorylation of IRS into IRS 1. And so that's just a reminder again from our previous lesson videos. Now also recall from our previous lesson videos that active IRS one really acts as a branch point, in insulin biosignaling. And so it can actually lead to many different pathways. And you might recall in our previous lesson videos, we saw active IRS 1 in insulin signaling on glucose metabolism. And here we're going to see active IRS 1 once again, but this time it's not going to be involved in glucose metabolism. It's going to be involved in growth factor signaling. And so again, IRS 1 can act as a branch point in insulin biosignaling and can lead to many different pathways, including this RAS pathway that we're about to introduce here. And so what is this RAAS here that the RAAS pathway is referring to? Well, Ras is actually a lipid linked monomeric g protein. But wait a second, I thought you said that g proteins were involved with GPCRs, g protein coupled receptors. Not with RTKs like the insulin receptor that we have down below. Well, it turns out that the Ras g protein is actually an exception to this. And so Ras is a G Protein that is not involved with GPCRs, instead it's involved with the Insulin RTK, a receptor tyrosine kinase. And so, another difference is in our previous lesson videos with the GPCRs, the g proteins were heterotrimeric g g proteins, meaning that they had 3 different subunits, the alpha, beta, and gamma subunits. But notice that this g protein here in Ras is not a heterotrimeric g protein. Instead, it's a monomeric g protein, meaning that it only has one single subunit instead of 3 different subunits. And so this Ras g protein, monomeric g protein, exists in 2 forms as you might expect. It exists in a GDP bound form, which is the inactive form, and it also exists in a GDP 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 RAAS pathway. And so really the ras pathway is a 3 step cascade of protein interactions, and these three steps really lead to the activation of this rasg protein during insulin signaling as a growth factor. And so notice down below, we have each of the 3 steps in this cascade numbered in our text, and of course, the numbers that you see here in our text correspond with the numbers that you see down below in our image. And so in the very first step of this RAS pathway, pathway, again, we're starting with active IRS 1, and so we're starting right here at this portion of our image. And so the active IRS 1 is going to serve as a binding site, as an adapter protein for the s h two domain of the adapter protein called g r b 2. And so if we take a look at our image down below, notice that IRS 1 over here is acting as an adapter protein, and the s h two domain of this protein right here, which is g r b 2, is, binding to the phosphorylated tyrosine residue on IRS 1, and this is going to activate g r b 2, which is another adapter protein. As we indicated up above that, grp g r b 2 is an adapter protein. And so this leads us to step number 2, and that is that grb two's sh 3 domain, which is on the opposite side of the protein, is going to serve as a binding site for another protein called SAWS. And SAWS, when it binds to grb2, it's going to form an IRS 1, grb 2 sauce complex since they're all binding to one another. And so if we take a look at our step number 2 down below, notice that the s h two domain over here of g r b 2 is binding to IRS 1. However, on the opposite end, we have an SH 3 domain on g r b 2 that is binding to this other orange protein over here that we're calling SARS. And so now what we have is an IRS 1, a g r b 2, and a sauce complex after step number 2, as we indicated up above. So then that leads us to step number 3, and, what's important to note is that the bound sauce protein is actually a guanine exchange factor, which you can see by these bolded 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 GDP, the low energy inactive form, with GTP, the high energy active form, on our ras monomeric g protein. And so notice down below in our image in step number 3 right here that we have this green protein right here, which is a monomeric g protein called Ras. And Ras is in its inactive state right here originally, where it is bound to GDP. But when sauce is bound to grb 2 and, sauce becomes activated, and sauce can then act as the guanine exchange factor that it is or the Geth that it is, and it's gonna catalyze the replacement of GDP with GDP to activate RAS. And so you can see that we have GTP replacing GDP here in the ras protein. And, of course, over here what we have is the ras bound to GTP, which is the active form of our ras monomeric g protein. And so this active ras will actually regulate cell growth via activation of another, signaling pathway called the mapk signaling cascade or the mapk signaling pathway. And so notice that here we're showing how RAS, the active form of RAS, 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 here actually concludes the ras pathway. The ras pathway ends with an active rasg protein. Now what's also important to note here is that very similar pathways to the one that we just discussed up above where IRS 1 activates GRB 2, activating SAWS, activating RAS. Very similar pathways can also be initiated by other signaling molecules other than insulin. So they can be initiated 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 ligand for this pathway, but instead, perhaps it is again epidermal growth factor or e g f or perhaps even p d g f, platelet derived growth factor, which again can stimulate very similar pathways to the one that we discussed up above. But this here concludes our introduction to the insulin growth factor signaling via the RAS pathway and we'll be able to get some practice applying this as we move along. And of course later we'll continue to talk about the mat k signaling cascade as well. So I'll see you guys in our next video.
3
example
Insulin Signaling as a Growth Factor Example 1
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Alright. So here we have an example problem that wants us to complete the sentence here using one of these 4 potential answer options down below. And it says that g proteins such as Ras are activated when, and of course, what we need to recall from our previous lesson videos is that Ras is a monomeric g protein, and it is an exception to other g proteins that are involved with g Protein Coupled Receptors or GPCRs. Because Ras is not involved with GPCRs. Instead, it's going to be involved in insulin RTK signaling pathways as a growth hormone. And so RAS, although it is found in these RTK pathways, 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 Ras 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 Ras are active. And And so we can go ahead and indicate that b here is the correct answer. Now a is incorrect because it says bound to GDP, but this is the low energy inactive form. And when Ras is bound to GDP, 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 Ras getting phosphorylated 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'll or this example and I'll see you guys in our next video.
4
Problem
Problem
In the insulin signaling pathway to activate the protein Ras, activated IRS-1 binds to ___________.
A
Adenylate cyclase.
B
SH2 domain of Grb2.
C
PLC.
D
GTP-bound Ras.
E
Insulin.
5
concept
Insulin Signaling as a Growth Factor
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So in our last lesson video, we said that the ras pathway ends with an activated monomeric rasg protein that ends up activating another pathway called the MAPK signaling cascade. And so here in this video, we're going to introduce what MAPK is. And so mapk is really just an abbreviation for mitogen activated protein kinases, as you can see by the first letter of each of these words gives us MAPK. As you can see by the name, these are indeed kinases themselves, and so they are going to be enzymes that phosphorylate their substrates. But more specifically, these Mitogen Activated Protein Kinases or MAPKs are enzymes that phosphorylate their substrates and lead to cell growth. And so what can remind us that these mapk's lead to cell growth is the word mitogen itself. Mitogens are really just a specific type of growth factor that specifically induce mitosis and cell division, leading to cell growth. Now what's really important to note about these MAPKs is that these MAPK enzymes can actually be regulated and phosphorylated by other MAPK enzymes. And so if we take a look at our example image down below of MAP Kinase MAPK Kinases, we will be able to understand this regulation in phosphorylation by other mapk's. And so let's say down below here in this green circle, this represents our mitogen activated protein kinase, our map k. And let's say that this map k, because it is a kinase, it's going to go on to phosphorylate other substrates. But if this map k is regulated by phosphorylation by another kinase, then this kinase right here in red would be referred to as a MAP k kinase because this is a kinase that phosphorylates the enzyme MAP k. And so more specifically, we could refer to this enzyme right here as a MAPK k, because it is a kinase that phosphorylates map kinase or map k. And if this enzyme right here is phosphorylated and regulated by phosphorylation by another kinase up here, then this would be referred to as the MAPK k kinase, because this is a kinase that regulates MAPKK. And so then this protein up here could be referred to as the mapkkk, and so what you end up getting is the mapkk regulates mapkk, and map K regulates MAPK, and MAPK goes on to phosphorylate the downstream targets that leads to mitosis and cell division. And so as we move forward in our course, we're going to see some specific examples of MAP KKKs, MAPKKs, and MAPKs as well. So keep this regulation here in mind. And so this here concludes our brief introduction to MAPKs. And in our next lesson video, we'll be able to continue our lesson on the MAPK signaling cascade. So I'll see you guys there.
6
concept
Insulin Signaling as a Growth Factor
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7m
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So here we're going to discuss how the ras pathway that we covered in our previous lesson videos activates the mapk signaling pathway. And so again, recall from our previous lesson videos that the ras pathway results in an active GTP bound ras protein that initiates another 4 step mapk signaling cascade. And so notice down below, we're showing you each of the 4 steps in the map k signaling cascade as a continuation of the 3 steps from the RAS 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 RAS pathway. And so notice that the first three steps here, step 1, step 2, and step 3 are shaded in gray because, again, these are the steps that we already covered in our previous lesson videos of the RAAS pathway. And so really the new steps that we're introducing here in this video are steps 4, 5, 6, and 7, which are really the 4 steps of the map k signaling cascade that we're introducing here in this video. And so of course these steps 4, 5, 6, and 7 that you see here correspond with the steps, the number of steps up above in our text 4, 5, 6, and 7. And so the very first step of the map case signaling cascade, which would correspond with step 4 here, is the active ras GTP from our ras pathway is going to directly activate a mapkk, which is a kinase that regulates a mapkk via phosphorylation. And this mapkk k here is actually going to be the protein called RAF1. And so if we take a look at our image down below at step number 4, again, notice that step number 4 is starting with the active ras GTP protein, that was the end result of the ras pathway. And so notice that this Ras this active Ras GTP protein is associating itself with this other protein called RAF 1, and RAF 1 is our map kkk. And so, really, that is it for our step number 4 right here, and that leads us directly into step number 5. And so in step number 5, the activated RAF 1 protein, this mapkkk, because it is a kinase, it's going to phosphorylate 2 serine residues on a mapkk called mek, mek, and this is going to activate mek. And so if we take a look at our step number 5 down below in our image over here, notice that RAF1, the mapkk, is regulating another mapkk via phosphorylation and this mapkk is mec. And so, what we can do is label mec as the map k k. And so notice that when MEK is not phosphorylated, it is in its inactive state. But as soon as RAF 1 phosphorylates MEK on these 2 serine residues, as we see here, the 2 phosphorylations, the 2 phosphate groups, MEK becomes active. And again, MEK is a kinase itself. And so this is going to lead us directly into step number 6. And so in step number 6, the active MEK, which is again this MAPK k, is going to phosphorylate the serine and tyrosine on a map k called ERK, and this is going to activate the mapk called irk. And so if we take a look at our step number 6 down below, notice that here what we have is our MAPK called ERK. And notice that when ERK is not phosphorylated, it is inactive, but upon being phosphorylated by the mapk k mec, it becomes active. And again ERK represents our MAPK, so we can label this as our MAPK right here. And so this leads us directly into step 7. And in step 7, as you can see in our text above, the active ERK protein is going to enter into the nucleus of the cell, and it's going to regulate the activity of transcription factors. These transcription factors that it regulates are specifically related 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 induce, 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 ERK, it turns out that ERK will actually regulate many different types of transcription factors. And so the ERK transcription factor targets actually include the transcription factors called ALK 1, SERF, JUNE, FOSS, and MYC, 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, 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 7 down below in our image, notice that the activated ERK protein, which is our map, k, our map kinase, In step number 7, 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 of, cell growth. And so again, the InsulinRTK signaling pathway on, as a growth factor includes the RAS pathway, which are steps 1, 2, and 3 here, as well as the MAP k pathway, which are steps 4, 5, 6, and 7. And so this here concludes our video on the introduction to how the RAS pathway activates the mapk signaling pathway, and as we move forward in our course, we'll be able to apply the concepts that we've learned. So I'll see you guys in our next video.
7
example
Insulin Signaling as a Growth Factor Example 2
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Alright. So here we have an example problem that says all of the following are true in the RAS and mapk pathways, except for which one of these 4 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 2 changes confirmation and binds to the next protein sauce in the signal transduction pathway. And so recall from our previous lesson videos where we called where we covered the RAS pathway that option a here is actually a true statement. And so after grb 2 binds to IRS 1, it's going to activate it and change its confirmation so that it can bind 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 RAS, 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 c says ras exchanges GDP for GTP and activates RAF 1, which is the first kinase in the mapk pathway. And so again, if you recall from our previous lesson videos where we covered the mapk pathway, that, this is actually a true statement. And so ras, we know, is a monomeric g protein, and the way that it becomes activated is by exchanging its low energy GDP for its high energy GTP. And the first thing that RAS does when it becomes activated is it activates another map kkk called RAF 1. And this is the first kinase in the mapk 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 on to option d here, it says the mapk 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 ERK, and ERK makes its way into the nucleus to regulate transcription factors that regulate 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 b 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 RAS? Well, that part of this answer is actually true. Sauce is used to activate the protein RAS. 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 GAF, 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 were looking for, we can go ahead and mark this as the answer we were looking for. And that concludes this practice or this example problem, and I'll see you guys in our next video.
8
concept
Insulin Signaling as a Growth Factor
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4m
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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 monomeric G Protein Ras also possesses GTPase activity. Now recall that the GTPase activity is really just referring to the ability of these G proteins to cleave or hydrolyze the high energy and active GTP into the low energy and inactive GDP. And so really, RAS's GTPase 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 ras's GTPase activity is that RAS's GTPase activity is actually very, very slow. So slow that it's actually actually not going to occur at a reasonable rate on its own. However, ras's GTPase activity can actually be sped up with the help from other proteins. And so these other proteins that help to speed up RAS's GTPase activity are called GTPase activating proteins or GAP for short or just GAP proteins. And so these GTPase activating proteins or GAPS as their name implies are just proteins that are going to activate the GTPase activity of Ras. And so they're going to increase the rate of Ras's GTP hydrolysis, which of course we mentioned up above is going to thus inactivate RAS. 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 RAS's g t p ase activity. And so notice over here on the right, what we have is the active Ras, which is bound to the high energy and active GTP. And notice that the arrow pointing to the left is showing the reaction that inactivates RAS, where it's going to hydrolyze the high energy active GTP into the low energy and inactive GDP. But again, Ras's GTPase activity is really, really slow, so it can only really occur with the help of other proteins called GAP proteins. And so here in this blank, we can fill in the gap and write in gap for these gap proteins. And so the gap proteins are going to help accelerate, RAS's GTPase activity where it will again cleave off one of the phosphate groups and, form the low energy inactive GDP. And of course, once RAS 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 these red arrows down below in our image, and all of these red arrows are really just referring to phosphatases, which recall are enzymes that remove phosphate groups and thus will reverse the kinase activity in this pathway. And so we know that the insulin signaling as a growth factor includes, the activity of a lot of different kinases that phosphorylate things. And so phosphatases are going to be really important to remove all of those phosphate groups, reverse the kinase activity and help 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 phosphatase activity, which removes the phosphate groups from all of these proteins and changes them to their inactive state. So you can see MEK here is being, the phosphatase activity is acting on MEK which is removing its phosphatase, its phosphate groups. And even IRS 1 phosphate groups can be removed by phosphatases and even the phosphate groups on the tire the insulin receptor domain, the Tyrosine Kinase domains can be removed as well. And so essentially, the main takeaway here of this video is that the removal of phosphate groups by phosphatases and by Ras' GTPase activity here when it cleaves GTP into GDP are really going to help terminate the signal and help reset the entire pathway. And so this here 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.
9
Problem
Problem
The monomeric G-protein Ras is activated by _______________, while _______________ helps turn Ras off.
A
Grb2 ; MAPK.
B
Sos ; GAP.
C
IRS-1 ; GAP.
D
MAPK ; Raf-1.
E
GAP ; Sos.
F
GEF ; Sos.
10
concept
Insulin Signaling as a Growth Factor
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5m
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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 and I'm gonna share with you guys a really creative and unique story that you'll only find here at 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 RAS pathway, and notice that it ends with Ras. And then of course the bottom pathway down here represents the mapk pathway. And so both the RAS pathway and the mapk 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 7 steps to this story. And these 7 steps that you see here correspond with the 7 steps from our previous lesson videos for insulin RTK signaling as a growth factor. And also these 7 steps also correspond with the seven numbers that we have down below in 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 only designed to help you guys memorize the most important components in the correct order. So because this pathway starts off with activated IRS 1, the first step of our story is that the IRS, the Internal Revenue Service, gives another tax refund. And again, that represents IRS 1. So if we take a look at our image down below, notice that step 1, 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, to buy 2 orders of wings on Grubhub. And so the two orders on Grubhub represents grb 2, the adapter protein that binds to IRS 1. And 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 2 here, 2 orders on Grubhub represents g r b 2. And this leads us to our 3rd step, and in our 3rd 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 going to add some hot sauce to the Grubhub wings. And so after the cell adds some hot sauce, he starts eating the food and all of a sudden the hot sauce starts to activate a rash, and the rash, of course, represents the monomeric RAS g Protein. And so notice down below in our image, step number 4, he's saying, I got a rash from eating those chicken wings there. And so in step number 5, the cell decides to call doctor Raphael, and doctor Rafael represents the map KKK called RAF 1. And so if you take a look down below, you can see that we've got doctor RAF here on the phone, since the cell's giving him a call, and he's, doc that leads us to step 6. And so doctor Raff says he's going to make, and making something represents the MATKK mec. He's gonna make the irking pain go away, and the irking pain, here represents the MAP k urk. And so you can see down below that doctor Raff tells the cell that he's going to make the irking pain go away. And so you can see we've got this irk pill here for step number 7. And, of course, the irk 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 full it can be really helpful for memorizing the most important components of this pathway in the correct order. And so by practicing this story just a handful of times you guys will get this down no problem. And so this here 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.
11
Problem
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 ______.
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?
A
The GAP protein will activate too many Ras proteins.
B
The Ras protein cannot be turned 'off' by GTP hydrolysis, so the signaling pathways remains activated.
C
The Ras protein cannot be turned 'on' so the signaling pathway cannot be activated.
D
The Ras protein is turned 'on' by the action of a protein kinase rather than GTP exchange.
13
Problem
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
A
Grb2 binds to the phosphorylated IRS-1.
B
Grb2 binds to the phosphorylated IRS using its SH2 domain.
C
Grb2 uses its SH3 domain to bind the GEF, Sos.
D
Grb2 binds directly to the serine residues of the insulin receptor's alpha-subunits.
E
The beta-subunits of the insulin receptor are phosphorylated on tyrosyl residues.
14
Problem
Problem
All of the following are true in the Ras and MAPK pathway EXCEPT:
A
The occupied growth factor receptor autophosphorylates serine residues.
B
Grb2 uses its Src homology 2 domain to bind to the phosphorylated IRS-1.
C
Grb2 binds Sos in the Ras signal transduction pathway.
D
In the MAPK pathway, Raf-1 phosphorylates MEK.
E
In the MAPK pathway, ERK regulates transcription factors that regulate mRNA synthesis.
15
Problem
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?
A
Signaling pathway increases in the presence of GAPs and decreases in the presence of GEFs.
B
Signaling pathway increases in the presence of GEFs and decreases in the presence of GAPs.
C
GAPs and GEFs both decrease the signaling pathway.
D
GAPs and GEFs both increase the signaling pathway.
E
GAPs and GEFs have no downstream effect on the Ras signaling pathway.