hi everyone in this video we'll talk about the ras map kinase pathway the map kinase pathway is initiated at the receptor level the receptors which are responsible for the signal transduction are cell surface receptor known as receptor tyrosine kinase because they have an intrinsic tyrosine kinase activity the ligands for these receptors are mitogens or the growth factors upon ligand binding the receptor tyrosine kinase dimerize this dimerized receptor is now active and it phosphorylates the tyrosine residues in the cytoplasmic domain now to this phosphorylated tyrosine residue specific adductor proteins can dock such as grb2 grb2 protein has sh2 domain which recognize phosphotyrosine residues now grp2 can further interact with sos protein sos protein otherwise named as sun of 7 less which was found in drosophila is actually a guanosine nucleotide exchange factor and it helps in gtp exchange sos actually helps ras which is a monomeric g protein to exchange its gdp and replace it with gtp and thereby activating the ras protein if you are wondering that why these proteins have weird names like sos grb2 then you should watch the video in i button it talks about the discovery of sos and the ras mapkin is signaling pathway however let's focus on this pathway for a while rest once activated now can dissociate and move in the membrane to interact with other kinases such as raf raf gets activated upon interaction with rash and in this moment we should understand that the activation of rash is not for a infinite time there are molecules like gap or gtbs activator protein which can hydrolyze the gtp and render the rash into an inactive state when ras is not bound to gtp raph is no more interacting with ras and the pathway would be eventually shut down anyway when rash is active raf is also active and it interacts with another downstream kind is known as mech and it phosphorylates make thus activating the make make further activates and phosphorylates arc art is another kinase which then translocates into the nucleus and interacts with several transcription factors and rna polymerase for and allow gene expression to happen and this is how the downstream cascade in wraps map kinase pathway takes place now let's talk about what are the genes which are transcribed by these pathway the genes that are transcribed by ras map kinase pathway are responsible for growth and cell division such as cyclin t1 also genes which are responsible for survival proliferation such as c meat bcl2 bcl excel all of the genes are the target genes for ras map kinase pathway from this gene expression profile we can understand rasnap kinase pathway give rise to growth division and proliferation in in terms of a tissue or a cell so overall ras map kinase pathway is very important for growing tissue or cells that are undergoing divisions now let me tell you a little bit uh details about this so one of the target gene of ras mapkins pathway is actually cycling d once cycling d is produced it interacts with its cdk partner that is cdk4r6 and cyclin d eventually phosphorylates prb protein prb under normal circumstances hold e2f protein which is an important transcriptional modulator and thereby preventing it to perform its transcriptional activity but cyclin d phosphorylates prb and allows the release of e2f e2f now can freely bind to the specific gene region and lead to the transcription of genes responsible for the s cell s phase of the cell cycle so overall we understand how cyclin d production helps in the progression of cell cycle from g1 to s and that kind of explains the growth activity of map kinase pathway now let me tell you in cancer ras map kinase pathway is perturbed one of the common thing in cancer is the mutation in ras oncogene in the mutated ras the gtpa's activator protein gap cannot hydrolyze the gtp as a result rash is constitutively active regardless the presence of any mitogen because it's a mutation in ras as a result the downstream effectors such as raf make arc all of them are active and the downstream of this pathway genes are actually transcribed this is leading to uncontrolled proliferation which might lead to cancer now we understand how ras mapkins pathway is responsible for cancer now let me tell you that when we think about ras map kinase pathway we always visualize the receptor tyrosine kinase to be the initiator of this pathway but this pathway can be initiated by g protein coupled receptor as well and that brings us with the essence of crosstalk between signaling pathways there are certain proteins known as beta arresting which modulates the g protein coupled receptor pathway can bind to these gpcrs and recruit a kinase known as src kinase src kinase can further phosphorylate arc and we know arc is downstream to map kinase pathway so obviously art can translocate into the nucleus and activate the genes which are responsible or which are important for this pathway which are important for growth survival or proliferation thereby we can appreciate how different pathways can crosstalk at different levels so with that let me say that if you like to support my channel do it on patreon if you're an indian viewer you can support me on a gpa or let's say veeam upi app your small contribution means a lot for me don't forget to like share and subscribe and my courses are also in academy which is india's biggest online learning platform in order to take my course use my code api