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Unformatted text preview: In the name of Allah Bio chem. Lec 17.1 How the signaling is turned off? This is the receptor complex called competent ( Signaling competent receptor ). This receptor has been activated how you can see that is activated because- it is dimmerize- the ligand is bind but the most impo is phospholipase of this tyrosine. This means this receptor is activated and signaling as readout we have - an activated STAT - transcription factor sitting on a gene ( SOCS gene ) .- And we want to turn off now The synthesis of the gene products of SOCS How we turn off the signal ???? what be intern tyrosine phosphorylation?? - reverse the kinase action by dephosphorylation via phosphatase ( Phosphotyrosine phosphatase SHP2 )--After recruitment, this enzymes by itself can recruited to the receptor at phosphotyrosine via SH2 domain 1. Now it can be acting on the neighboring molecule which has phosphotyrosines which means o activated Jak and o activated receptor. So the recruitment need also the the phosphotyrosine. Then it cleaves the phosphates from the Tyr because it can reach the yanus kinase at phosphotyrosine. o So the yanus kinase is no more active because phosphatase has cleave off the phosphate and the similar thing happens to the receptor. o The receptor phosphate is cleaves off from the tyrosine so nothing can be recruited anymore to the receptor. For Eg the phosphotyrosine which recruited the STAT factors and the STAT factor was activated and also tyrosine phosphorylated . 2. The SHP2 can also dephosphorylate the STAT. o And then the transcription factor is not activated anymore. In the case of the STAT - here you see the phosphate in this form the STAT is a dimmer - it is active - It is going to move to the nucleus But if phosphatase comes phosphatase cleaves off the phosphate Other phosphatase - where do we need the action of phosphatase? ( kind of the signaling cascade . In the nucleus , act at the STAT nuclear tyrosine phosphatase called T- cell(specific nuclear phosphotyrosine phosphatase “the name not so impo to know”- It localized only in the nucleus not anywhere in the cell - It can attract the phosphotyrosin in the STAT dimmer and dephosphrated it - the dephosphrated STAT can be o by protosomes degraded protyolytically o or exported by the NPC “nuclear pore” and reused to be activated for further activation of the cascade The protosme :- It is an organelle which you found in the cytoplasm mainly and in the nucleus - It is the place where most of the proteins in the cell are degraded - Every protein have turn over the ptn turn over is more or less regulated by a protosome action ,...
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- Spring '10
- receptor activation, IL-6, IL-6 receptor