13066012
Description
Flashcards by J yadonknow, updated more than 1 year ago
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Created by J yadonknow
about 6 years ago
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| Question | Answer |
| Enzyme linked receptors | Tyrosine Kinase Receptors (TKRs) |
| TKRs | 1. EXC domain binds ligand. 2. Transmembrane domain 3. IC domain, has TK 4. +Pi Tyr residues from ATP |
| PK casses | TK serine/threonine kinases e.g. PKA/B/C |
| Binding to PK | 1. Ligand binds to monomer 2. Induces conf. Δ in EC dom., dimerise 3. Induces conf. Δ in IC domain. 4. Auto-Pi,reveals substrate BS on opposite R 5. Transphosphorylation. 6. +Pi-Tyr provides docking site for signalling molecule. |
| GF R signalling | +Pi -> Grb2 -> SOS -> Ras GTP |
| Insulin R signalling | 1. Unusual as adaptors are +Pi by receptor themselves. 2. +Pi on IRS provide docking sites for a multitude of signalling cascades. 3. Compensatory mechanism as Insulin R doesn't have many Tyr in IC domain. (extension cord). |
| Ras | Monomeric G protein (acts like alpha SU) + When bound to GTP Intrinsic GTPase activity to - Accessory proteins required to cycle between +/- |
| +/- of Ras | GEFs -> + GAP -> - (Cycle) |
| Ras signal cascade | Ras Y-Pi -> Grb2 -> SOS -> Ras-GDP -> Ras-GTP -> MEK _MAPK -> +Pi-TF Ras-GDP -> Ras-GTP (SOS) Ras-GTP -> Ras-GDP (GAP) |
| Insulin Receptor | Only TK to not dimerise Heterotetrameter in PCM Alpha SU bind to insulin Induces conf. Δ in TK -> trans/auto+Pi |
| Insulin R cascade | Insulin -> Alpha -> trans/auto-> IRS-1 -> PIP2 -> PIP3 -> PDK1 -> PKB -> Glut-4 vesicle translocation |
| Why do this? | Regulates glucose uptake Vesicle translocates to PCM, fuses, takes up glucose, passes it back into cell. |
| Enzyme -linked R | Recruit EZ from cytoplasm e.g. Cytokine R recruit JAK to help initiate cell signalling |
| MOA (6) | 1. Cytokine R lacks intrinsic K activity. 2. Recruit soluble TK i.e. JAK. 3. Ligand binding causes R dimerisation + JAK+ 4. JAK + each other and R 5. Adaptor proteins recruited to +Pi-Tyr on R OR 6. STAT TF directly to JAK |
| Preferable drug design | Small molecules favoured |
| The protein | domains capable of strong+specific interactions w/ drug Has cavity e.g. well defined catalytic cleft |
| Good/Bad targets? | Good: R/EZ Bad: TF (apart from Nuclear R's). |
| Common target | Competitive binding to ATP binding region to prevent gamma-phosphorylation |
| Nuclear Receptors | Ligand + TF |
| Domain Structure: | Mod. conserved ligand-binding dom. Highly conserved DNA binding dom. Highly variable N-term w/ 1(>) + Domains |
| Categorisation 1 based on MOA and distribution in cell when L absent (5) | Category 1: Steroid/androgen R. Found in cyto associated w heat shock protein Forms a homodimer Once in nucleus recruits co-+'s to mod. chromatin/DNA Pol' activity. |
| Category 2 | In nucleus Sit on response cell event (DNA) Form heterodimer, always complexed to RxR Core repressor keeps chromatin compact, preventing gene transcription. |
| Category 2 diagram | Yoooohohoho |
| Anti-hormone drugs | e.g. Tamoxifen Struct similar to hormone, binds to LBD Allows R dimerisation + binding to DNA/gene promoter Side chains rpevent correct structural rearrangement of R Co-activator BS is BLOCKED. |
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