IMM350H1 Lecture Notes - Lecture 5: Ubiquitin Ligase, Ptpn6, Ubiquitin
Document Summary
Signal amplification molecules at membrane: amplification by kinase cascades, binding to phosphorylated sites on membrane associated protein (ex: lat, recognition of activated small. G proteins (ras active when bound to gtp: raf mapkkk, mek mapkk, erk - mapk, secondary messengers can diffuse and activate downstream molecules, binding to membrane lipids (pi3kinase phosphorylates. Pip2 to pip3) **pip3 short lived to prevent excess signalling: ca++ diffuses throughout cell inducing conformational changes in calmodulin. Cd3 complex is noncovalently associated with tcr through. Turning off the signal: dephospohorylation of phosphorylated substrates (ex shp-1. & 2: ubiquitin-mediated degradation by proteasome, ubiquitin-mediated degradation in the lysosome. Signalling through cd28 (costimulatory molecule) charged aas in the transmembrane domain. B7. 1 and b7. 2 are cd28 ligands expressed on apcs. This activates pi 3-kinase to produce pip3. Pip3 recruits itk, allowing it to phosphorylate plc-y. Lck phospohorylates zap70 (normally autoinhibited by sh2 domains) Phosphorylation on serine and threonine residues keeps nfat in cytoplasm of unstimulated cells.
