BIOL 4610 1st Edition Lecture 18Outline of Current Lecture 1. Receptor-mediated endocytosis2. Phosphotyrosine phosphatase3. Feedback inhibition4. No Wnt signal5. Wnt signalCurrent LectureHow do you turn off RTKs and cytokine receptors?1) Receptor-mediated endocytosisa. Cytokine receptors: like erythropoietin b. Endocytosis: clathrin vesicles c. Signal binds the receptors à reveals a sorting signal for vesicle recruitmentd. - Cargo is broken down in the lysosomee. About a ten fold quicker turnoverf. Removes the receptor form the cell membrane2) Use a phosphotyrosinephosphatase (SHP1)a. P- Tyrosine residues on the receptors act as docking sites for other proteins b. -To prevent docking, remove the tyrosine residues or phosphate groupsc. SHPI: a phosphate group off of tyrosine residuesd. SH2 domains- bind to P tyrosines; in an active ste, SH2 domains cover up the active phosphatase sitee. Phosphate domain: cuts P off activation Lips3) Feedback inhibitiona. SOCS proteins are transcribed by cytokine pathways b. SOCS block the phosphorylatestyrosines on the receptors by binding to them.c. SOCS box domain: recruits a ubiquitin ligased. This leads to degradation in proteasomesThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.16.5. Signaling pathways controlled by ubiquitination: WntPathwayUbiquitination: degradation!Cell differentiationWnt pathway: Development of nervous system and brain, important in muscle development, bone formation, also controls overalpetterning of the body (where parts are supposed to go)Signals are called Wint proteins: theings that are secretedd from cells and then modified. Modification is adding 2 16-carbon fatty acyl chain onto the protein (look like lipid-anchor proteins- doesn’t go far; associated with cell membrane)When no Wnt signal àdegradation of b-cateninReceptor is frizzled- can bind to Wnt proteinHave complex of proteins. The key protein is beta-Catenin: will go into the nucleus and act as a transcription factor. When signal is not around, B-Catenin is held back in the cytoplasm, and held by a scaffolding protein called Axin. Scaffolding means it’s multi docking and can hold more than one thing. Also holds GSK3, CK1 à Kinases**GSK3 and CK1 phosphorylate B-Catenin and this targets it for proteasomal degradation. **Summary: When no signal present – B-Catenin degraded all the time. Wnt signal àb-catenin acts as a co-transcription factorWnt binds to frizzled receptor and co-receptor LRP à recruits Axin out of cytoplasm up to the plasma membrane.The kinases are then not attached to B-Catenin and can’t phosphorylate it and therefore is not degraded. So, B-Catenin can go into the nucleus and act as a transcription
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