all right welcome back so in this particular video I want to explain to you how a kinase cascade works okay so we're gonna have multiple kinase as working together achieving two things one signal integration so that many different things can be achieved with one pathway okay and two amplification where we go from one protein to many proteins from one key player to many key players to really spread the message effectively alright so remember as wrasse is sitting right here at the plasma membrane and we now have to amplify the signal shout it out that everybody in the cell gets it and then have very specific responses right here right so we might to have to modify some proteins turning them from act inactive to active you might have to modify some transcription factors that can end up in the nucleus and make more proteins right so all these things need to happen that's the integration hitting many many different responses right here okay the amplification happens right here I'm gonna call this cascade right here a mitogen-activated protein cascade well map kinase cascade okay again these can have specific names and in your book and you saw that that I'm gonna put them on the slide so you know what I'm talking about okay so first things first wrasse is activated has the high energy gtp in it and activates this first kinase in the serious near the plasma membrane where it resides okay and from there this kinase signals this kinase signals this kinase and this 3 kinase signaling right here serves to amplify the signal because when we have a touch event when one protein interacts with another protein by attached like I said it's the one the one there's no amplification when we have covalent modification however specifically phosphorylation right here you one protein one kinase can phosphorylate many kinase or many other proteins downstream it's like you know it's like Oprah and you get a kinase and you get a coyote you get a phosphate and you get a phosphate and you get a phosphate and so within a very short amount of time a single kinase can activate hundreds of proteins at the same at the same time and that amplifies the signal that goes like one kinase activates a hundred kinase those hundred kinase is activated a hundred kinases each and you can see how the zero is a building up here at the end we get a number that is astonishing so we can go from a single rass protein right here that activates the first kinase by attached to a hundred million copies of that last kinase that is responsible for activating these target proteins so that's the amplification of the signal okay and so we're gonna start with the last one this last kinase that's actually my map kinase my mitogen-activated protein kinase it does what it does best it takes a phosphate from ATP and it sticks it on target proteins in this case it activates protein X Y and transcription factors a and B so again either protein is present it just needs to be turned on or a protein has to be made in which case a transcription factor has to been full has to been activated this nap then goes into the nucleus and turns on usually binds to a response element same thing as we saw with estrogen receptor and turns on the expression of the target genes that need to be expressed alright I say one thing about regarding nomenclature nomenclature is kind of backwards here so this is my map kinase that's what it was called enjoy in your book okay and so the protein that turns on map kinase that turns it from an inactive map kinase to an active one is another kinase and in the way map kinase is turned on the way this orange protein is turned on is by sticking phosphates on that do you see that so map kinase put these phosphates on these target proteins map kinase got activated when map kinase kinase put these start these fossil phosphates onto it okay so the way a kinase is named generically now it's mek in the pathway right but the way that generic kinases work is that your last K stands for kinase that's its job okay that's what it does it puts phosphates on someone the first part anything before that K is the target onto which it puts that phosphate okay so map kinase kinase last one tells me the job this tells me the cargo protein so when I read this I know that this blue protein sticks a phosphate phosphorylates map kinase because that's what's written right here now again then that meant mean raff right here is actually also called map kinase kinase kinase why because it's a kinase that's what the last K tells me that specifically phosphorylates check out these two phosphates of map kinase kinase so that's how they that's how the nomenclature work so the first time you read a signal transduction paper you're like what is up with the case and that's the explanation right here again the last K designates the job anything before that designates the target protein so if I was a target protein the kinase that would put a phosphate on to me would literally be called dr. Boudicca kinase because you get a job and it's hard we got it all right so that's where we have the amplification wrasse can activate mat KKK which can in a very short amount of time activate many molecules of map and these in turn can turn on many molecules of map k and so that's where the signal amplification happens the integration is right here that that last kinase can a phosphorylated number of different target proteins to bring about a number of different effects if you imagine when a cell undergoes cell division or prepares for it a lot of things have to happen so remember in the one the first lectures that we have we talked about hey in mitosis first a nuclear envelope dissolves and the chromosomes condensed all these things are orchestrated by kinase --is okay literally the way the nuclear envelope dissolves is when a kinase puts phosphates on the proteins that are on the inside of the nuclear envelope at the nuclear lamina which then means because phosphates are negatively charged they put a pressure on it they repel one another and that's what rips the nuclear envelope apart and when you take these phosphates back off the nuclear envelope reestablishes so again we're talking about a like all these things that you think of happening in the cell cycle are orchestrated by a kinase leave it at that and then lastly again bring it back so if Rass is frequently mutated right what do you think these mutations do in grass the answer is it doesn't allow rats to turn itself back off it doesn't allow wrasse to exchange that gtp or they turn a gtp back into a GDP to become silent to become non active and so an overactive wrasse that's what makes wrasse more the most commonly mutated oncogenes it's wendy GTP hydrolysis activity of this off wrasse protein is mutated and so it would always always signal mat KKK in this signal transduction pathway it would be stuck in the on position and that would be bombed by the way these can be separately mutated if Matt KK was mutated it would still have a constant expression so all of these are proto-oncogenes and they can mutate into an oncogenes when they get stuck in the on position and constantly signal the cell to proliferate and survive