Biosignaling 3

just like cyclic, and he has a bunch of functions in the cell. G also carries out a wide variety of functions and cell signaling, and in addition to activating the den, real cyclists, G protein with GTP bound will also activate fossil ape A C, which is an enzyme you might remember from the last unit and this enzyme cleaves lipids. Hopefully, you remember specifically where it cleaves lipids as that's something that we covered for the last exam. Now fossil apes see, um, in the case of cell, signaling will cleave the bond between the innocent it'll phosphate and the glycerol of the molecule phosphate title in a hospital or abbreviated as P. I P two. And you can see that happening right here we have our G protein coupled receptor with lagon bound and that this little lightning bolt saying it's that G is activating fossil. I pay C p l C what we see right there, and that's going to cleave this molecule p I p. Two possible light are sorry phosphate title and no settle, and it's going to cleave it into, um, what's abbreviated as I p three or in Oz, It'll triphosphate what you see right here and it's, uh, also the other. Sorry, I should say the other part of the molecule after its cleaved is called day. So glycerol or D A G. So just to recap, fossil like Pacey gets activated by G and it cleaves pipe too into D A. G and I p three. Done. Um, just thio note quickly that, um d a g will stay in the membrane, whereas I p three will, uh, like exit the membrane Azaz. It is able thio, uh, interact with water much better. The other is, you know, very hydrophobic lipid. But I p three has those phosphate groups meaning it's gonna have a lot of charge so it can interact with water very nicely. So in a Seattle triphosphate will actually go diffuse into the cell and it will open up these calcium channels. So here's some sort of internal cell membrane. It's going thio activate these calcium channels so that calcium gets released and die a slow glycerol and calcium. These guys will actually lead to the activation of protein kindness. See additionally, a nostril try phosphate and calcium will act a secondary messengers in a variety of other signaling pathways. But just know that calcium and diocese glycerol will activate protein kinda see. And no, um, you know, how are how the cleavage of phosphate title in a Seattle leads Thio D, A. G and I P. Three. Moving on spent a lot of time on G protein coupled receptors. Now let's actually take a look at a different type of receptor called receptor tyrosine, kindness or RTK, and these air receptors that are capable of auto phosphor relating meaning they can fuss for late themselves, and they'll do so at a tyrosine residue. And, um, or I should say residues. And they'll do this in response to Lijun binding. So we're going to look at insulin as our example of an Arctic. Are the insulin receptor rather as an example of RTK and the insulin receptor actually works best as a dime er and you can see that we have nice protein dime er right there, meaning that you know, we have these two halves basically coming together, Thio our dime arising and forming this nice protein dime er that we see they're acting as a receptor and here we have insulin. That's our wagons and insulin is going Thio bind into our receptor and thats going Thio initiate phosphor relation Cascade. So, um let me hop out of the image here so we can see happening is, uh this is that tires in kindness domain So it's going thio auto focus for late and can see here that it is going to have a bunch of phosphate groups attached to it. And thats going thio lead to the foster relation of a bunch of proteins you see here, here and here. So, um specifically with insulin, the insulin receptor after it uh, is phosphor related It's going thio foster for late a protein called IRS one and I rs one is going to turn on this wrasse protein complex so it's a complex of proteins, Um, kind of like all bound together. IRS one is gonna turn on rass the wrasse protein complex, the wrasse protein complex phosphor relates Maek Maek phosphor relates ERC and ERC enters the nucleus and activates genes. So basically insulin binds the receptor tires and kindness does its auto phosphor elation and this generates a phosphor relation cascade which ultimately leads to this protein IRQ entering the nucleus and activating certain genes, leading thio the expression of certain genes. And anyways, IRS one also activates protein kindness to be right. So hopefully you're starting to see a pattern here that all of these components of signaling pathways tend to do multiple things right. They don't just have, like, one simple job. So anyways, IRS one also activates protein kindness be, and that ultimately leads to more glucose transporters, specifically, Group four transporters in the membrane. So let's back up and think about this for a second. So insulin is released in response to you high sugar levels in your blood. So when Insulin's released, it's gonna bind to this receptor tire, seen kindness and activate a bunch of genes related thio Um, you know, related to processing this sugar. Basically, additionally, it's gonna activate protein kindness be and protein kindness be is going to put these glucose receptors in the membrane thio, um, transport into the cell. This high concentration of glucose, that is, um, that is present outside the cell, right? Like in the blood. So, you know, thinking about it on ah, more medical level. You know, we often say that insulin lowers blood sugar levels well, this is partially how it's doing that by increasing the number of glucose transporters in the membrane, thereby taking sugar out of the blood and putting it in the cell. Additionally, insulin causes glycogen formation because, you know, you have this excessive sugar. You want to store some of it for later because you don't need to burn all of it right away for nutrients. So protein kindness be in addition Thio causing those glute four receptors thio, um be integrated into the membrane protein. Chinese B also leads to the activation of glycogen synthesis and the way it does that, is it actually in activates G s K three or glycogen synthesis kindness or the G S K is so it alright in activates GS K three and that allows glycogen synthesis to become active because it's now this is where things, you know, maybe get a little confusing. So G s K three is normally a new active protein and its job is to inactivate glycogen synthesis. So normally it's g s. K three is on, and it's keeping glycogen synthesis off, and it does this by phosphor relating it right. Here's, uh here's a great example of where phosphor relating something, actually in activates it. So G s K three keeps like John Synthes off by phosphor relating it. But when protein kindness be comes around it phosphor relates GS K three, which in activates GSK three and that allows glycogen synthesis to actually become active and synthesize glycogen with all that extra glucose. And remember, a lot of glucose is getting transported into the cell now because of those extra glucose transporters. So you can see how this one ligand, right? Insulin is doing a wide variety of things in the cell. But they're all kind of related to this central theme of trying to do something about all that sugar. So hopefully that kind of helps illustrate a little bit how, you know, expansive these signaling pathways are and how they can integrate into one another. All right, let's flip the page.