The MAP-Kinase (MAPK) signalling pathway

[@mrinalino]

I'm having cancer biology this semester and this was hugely helpful for understanding the basics...thanks a ton.. :)

[@xXCaiZeXx]

I just recognized that no video here on youtube shows that MAPKKK (Raf), MAPKK (MEK1/1) and MAPK (ERK 1/2) are kind of "fixed" on scaffold proteins near the membrane (scaffold protein: KSR) or other cell areas (other proteins)...that would be a nice addition, besides that, this is the best video I've seen so far!!

[@GronTheMighty]

Although the topic of my exam today is the effect of mutations in the KRAS gene which inhibits response to EGFR-supressing monoclonal antibodies, this animation still was rather helpful in ensuring that my understanding of the general pathway in question is intact and functional - Thanks to the makers/uploader

[@karengoh1982]

MAPK pathway begins with binding of ligand to receptor e.g. EGF to receptor tyrosine kinase Ligand binding leads to dimerization of subunits of receptor tyrosine kinase at the inner side. Tyrosine kinase domains catalyse phosphorylation of itself GRB2 bound to phosphorylated RTK Protein SOS bound to RAS Active RAS bind to GTP Active Braf phosphorylates and activate kinase MEK1/2 which in turns phosphorylates ERK 1/ 2 and kinase cascade leads to activation of transcription factors AP1, move to nucleus, form a heterodimer and bind to DNA, leads to expressions of genes and coding thus leads to cell proliferation. B-Raf GTP is inactivated by GTPases activating protein, GAP. GAP binds to Ras GTP and increases the weak GTPases activity GTP is hydrolyzed to GDP and Ras is inactive and cannot bind to Braf. Therefore MAPK signaling pathway turned off. Mutated active Ras GTP is also able to bind and activate Braf However mutated Ras loses ability to be inactivated by GTPases activating protein, GAP. GAP can bind to Ras GTP but cannot hydrolyze GTP to GDP therefore activating MAPK signaling pathway and leads to non-stop cell proliferation

[@gitgud1536]

+Karen Goh Ligand binds to LBD > > receptors dimerize > > trans-autophosphorylation of TK domains and Tyr subunits on the cytoplasmic tail > > GRB2 interaction with phosphorylated TK domain via SH2 site > > GRB2's SH3 site recruits SOS and interacts with SOS's Proline rich domain > > SOS recruits RAS > > RAS exchanges GDP for GTP > > RAS recruits RAF/14-3-3 complex > > PP2A cleaves inhibitory phosphates from RAF & removes 14-3-3 inhibitor > > Src Tyr Kinase phosphorylates RAF > > RAF a Ser/Thr Kinase phosphorylates MEK > > MEK double phosphorylates ERK at Thr & Tyr > > ERK translocates to nucleus and phosphorylates Elk1 > > Elk1 acts as a transcription factor for the production of C-FOS > > C-FOS and C-JUN form hetrodimer > > Hetrodimer binds DNA at AP-1.

[@samuelgreenrod1812]

I also learnt the FGF also forms a complex with the extracellular proteoglycans

[@kirissapadilla5905]

Thank you for this! So much easier to follow when animated than staring at my textbook or powerpoint slides.

[@AutumnTeaLeaves]

I listened to it on 2x speed and it was perfect. I thought it was very helpful. Thank you for this video.

[@tilapia_guitar]

show off

[@evil-robot]

Very clear and (more improtantly) memorable! I especially like the bit at the end on tumorigenisis.

[@ashleeharrison9439]

Wow, exactly what I needed to know and explained so clearly. Many thanks!

[@tankx2]

This video is absolutely brilliant.. my lecturer is Italian and its very difficult to tell what she is saying.. this has saved my life!

[@mekamalika]

got though lots of pages in the text book to get through with this very simple process ..may be worked on it for an hour or two .. but here only 6 min.s got it through to me... you tube's a blessing......what would have happened to me if you tube won't have been there.... it's very useful ....

[@petercourt]

This is brilliant, just what I was looking for! Thanks.

[@bogdanchivagiurca3633]

Thank you very much. This video is perfect. Very well explained.

[@nmkadhim]

This has helped me so much.. Thanks!

[@JongensJavaanse]

great explanations, I'd wish you'd have more videos like this for example on the hedgehog signaling pathway!

[@Inyashikewoo]

I don't know if you still need it but here is a really good one: kzbin.info/www/bejne/nKu5lH1tm7yljMk he has a lot of good videos about other subjects as well. Hope it helps.

[@MrSatish59]

great video!thank u:)helped alot... i'd like watch this every week!

[@OneLove172]

The best bio video I have ever seen

[@rbrtchng]

This will save me on my midterm tomorrow

[@alicemacf]

This just saved me about 2 hours trying to understand what the heck my signal transduction book is trying to say.

[@jorgedlgg]

@paulioyeuh the original receptor is only activated with bound ligands and loses affinity for them afterwards. So no, the receptor is not activated all the time.

[@isthis1t]

This is going to come into use in my final tomorrow. Thank you!

[@abhoriel]

fantastic animation, many thanks

[@mclarros]

Well explained, thank you!

[@mazaeducation]

+Maria Claros can you explain me ?

[@LiMeiLuv]

+Hamza Elhassouni lh3.googleusercontent.com/-dun2pamQ6ek/AAAAAAAAAAI/AAAAAAAAAFw/RuZSsvWAr50/s60-p-rw-no/photo.jpg

[@zannatul23]

thank you, helpful summary

[@jamesshaffer5589]

Great explanation!

[@olgapawlik474]

This is the best video for this

[@Muuip]

Thank you! very well explained.

[@MG-xn5uw]

it is so helpful!!!Thank you

[@ramaanouz1607]

That's helped a lot 🌺 thanks

[@rsinsights17]

Really it is helpful.............Thanks a lot!

[@helenateixidor6932]

Very helpful, thanks :)

[@redSHIFT69]

SOS = son of sam ? idk. i m in med school and have a test on this stuff tomorrow. 1 of 100 cascades i have to remember....on another note. how many biochemists does it take to change a light bulb?

[@CexyNariko]

Thank You so much!!!

[@annekokke7898]

Why is the SOS protein recruited to GRB2? It feels like there's a step missing. How does RAS activate B-Raf; by phosphorylating it?

[@avao]

This was very helpful!

[@mairajalil3565]

so Receptor tyrosine kinases are involved in autophosphorylation and also in transphosphorylation (of the other receptor)(in dimer). is this true?

[@gitgud1536]

Hold on.. after ERK activation doesnt it dimerize and translocate to the nucleus where it in turn phosphorylates Elk1 or C-myc which act as transcription factors FOR C-FOS transcription by RNAPoly II and then the C-FOS/C-JUN hetrodimer can be formed?

[@adaptationmec]

very nice and useful. thanks alot.

[@tartanhandbag]

im under the impression that SOS translocates to the membrane, but this is not depicted?

[@fabiolaguadalupeperaltaver3493]

Good video ;) Thanks alot

[@myexentrikrevolution]

I was hoping to hear about MAPKKK, MAPKK, and MAPK in regards to ATP/ADP...

[@BekahIceAngel]

myexentrikrevolution Mapkkk is raf , mapk is mek and mapk is erk

[@myexentrikrevolution]

THANK YOU!!!

[@mazaeducation]

+Bekah Dents can you explain me this video in schema ? plz

[@MrLago92]

Beautiful

[@kappasr]

Thanks, it's very useful and clear =)

[@goodvibesnerd3228]

Thank you ☺

[@wiamalbouzidi8362]

Thank you ! :D

[@raissamelo8055]

Thanks a lot :)

[@brightminji]

MAPKKK = B-Raf, MAPKK = MEK1/2, MAPK = Erk 1/2 :) Erk 1/2 is phosphorylated and activated by MEK 1/2, which in turn are phosphorylated and activated by B-Raf.

[@pablovicruiz3281]

jesus de veracruz. Excelente pinche animación, se la rifan bien pesado.

[@AbrarPharm]

thank you , very informative video :)

[@5surfinbird]

THANK YOUUUUUU!!!

[@oforiagyeman]

Is the cctivation of the MAPK pathway produced by Receptor tyrosine kinase and cAMP?

[@fknlife]

Why cAMP?

[@APS129]

cAMP is generally for the regulation of Protein Kinase A (PKA). So I don't think it has a role in this specific pathway

[@Maderr4]

Thanks!!!

[@kataka88]

thank Allah for this video may god bless u

[@PrettyPrincessSharz]

LIFE SAVER.

[@karengoh1982]

do u have the proper captions or text? thanks!

[@abdulkhaleqalkadimi813]

thanks a lot

you are welcome!

[@delic619]

@joshua99999999 Awesome man! I bet you are heaps good at reading chapter books and long division? I'm sure you can tell me what an atom is made of too?!!!

[@catawingfield1898]

What does JUN and FOS stand for?

[@WolfgangDibiasi]

EXAME tomorrow, wish me luck^^

[@MsAnthropicsRhapsody]

There should be 2 ligands for 1 receptor dimer.

[@BeeYouLah]

False

[@BeeYouLah]

False

[@Legendnos]

Merci😇

[@arujunan]

thks to god for this animation

[@delic619]

@Gottfried2210 dude, i reckon if you explain signal transduction pathways that way in an exam, you'll get bonus marks...

[@houssposey8027]

first, thank you so musch i'm now a fucking biochimist

[@sanxxxx]

Biochemistry exam sent me here.

[@salmonnnnman]

@kommienzuspadt Yeah i hear that, superiority complex, i see it with people on my course too. Seem to think because we do a science degree that suddenly any other degree has 0 value. Particularly pisses me off when they go after musicians or artists claiming there skills to be useless. Absolute arrogance.

[@delic619]

@joshua99999999 Pretty cool story bro. Good call though, biochemistry would probably have been too hard anyway...

[@redSHIFT69]

go RAS go!

[@darkclaw999]

May youtube god bless this xD

[@neighborhoodman323]

Onkoview.... more like ONCOview

[@shreds941]

lmao! @ 4:10

[@maxjohn9640]

How can anyone find this helpful? It's rushed, the voice grates on the brain, and the pronounciation of various factors is constantly in flux!

[@sydanaya]

nope its actually pretty good

[@maxjohn9640]

Surely you can back that opinion up with some specific facts regarding the source of the "goodness"? What specifically is pretty good, in light of my specific criticisms?

[@sydanaya]

Well its a good short summary, i compared it to my cellbio book and it helped me understand the pathway... The voice is clearly not a computer generated voice.. And let me know if you find a better Video on youtube

[@danwaters7665]

big dog

[@Maderr4]

HILLLLLLARIOOOOOOUUSSSS!!!!

[@kommienzuspadt]

@pedromigelab You misspelled three very basic words. Please consider brushing up in your mastery of the english language before you go handing out condescending remarks to other people. Your mistakes would be shameful for most middle schoolers.

[@starzhisoka6346]

Fuck me. Who wants to be a doctor anyways?

[@adaptationmec]

very nice and useful. thanks alot.