Protein Receptors Flashcards
- Tyr-Kin Receptors:
- EGFR Tyr-Kin Activation Cascase? (7 steps)
- 2 main therapy types:
1. ) Antibody: Works how? Ex?
2. ) TKI’s: Work how? Ex? Only works for who? Then what happens? Ex? Other possible RTK pathways the cancer may find? - Best treatment practice?
- What if mutation is down stream? Ex?
- ) Ligand binds 2.) Homo/hetero dimerization 3.) Catalytic activity of kinase on ATP 4.) Autophosphorylation 5.) GRB2 Binds 6.) SOS (a Ras GEF) binds 7.) Proximity to membrane bound Ras leads to guanine exchange to RAS-GTP
- Block ligand binding to prevent dimerization; Cetuximab
- Blocks ATP substrate binding; Gefitinib; people with EGFR point mutations on receptor; acquired resistance; Gatekeeper mutation allows ATP but blocks drug; ERbB2 or MET
- Use combos
- Drug won’t work; KRAS mutations
- G-Coupled Protein receptors:
- Structure? Ligand binds where? 3 sub units? Activation leads to? RDS? What dissociates? a subunit acts as what? Leads to?
- Effect of pertussis toxin? Cholera toxin?
- Sympathetic branch receptors? Stimulus? Ex? (2) Proteins? Effect?
- Parasympathetic branch receptors? Stimulus? Ex? (2) Proteins? Effect?
- 7 transmembrane helical domains; in pocket of a helices; a,B-y; nu- exchange of GDP for GTP; yes; Ga-GTP and B-y; GTPase; hydrolysis causing subunits to return to receptor
- ATP ribose locks a subunit = no activation; ATP ribose inhibits GTPase = no deactivation
- Adrenergic; NE; 1.) B1AR - Gs protein –> stim. AC and cAMP production 2.) a1AR: Gq –> stim. PLC, Ca and lipid signals
- Muscarinic; Ach; 1.) m2AChR: Gi –> Inhibits AC 2.) M3AChR: Gq - stim. PLC, Ca and lipid signals
- G-Coupled Protein receptors:
- B1AR (heart)? (7 steps) Antagonist?
- a1AR? (5 steps) Antagonist?
- m2AChR (7 steps) Antagonist? Why does cAMP decrease? Drug example?
1.) NE binds 2.) Gsa-GTP becomes active 3.) Gsa-GTP binds AC 4.) cAMP increases 5.) PKA activated 6.) Ca channels open 7.) Inc. HR/Contract
(Metroprolol)
1.) NE binds 2.) Gqa-GTP becomes active 3.) Acts on PIP2 to create DAG and IP3 4.) IP3 –> Inc. Ca; DAG –> PKC –> LCH –> Ca inc 5.) smooth muscle contraction; (prazosin)
1.) Ach Binds 2.) Gia-GTP becomes active 3.) Deactivates AC 4.) Ca decreases and so does HR 5.) By released 6.) BY activates GIRK (K= channel) 7.) Hyperpol. decreases HR
- PDE turns it to AMP; Caffeine
- G-Coupled Protein receptors:
- Second message examples? (3)
- Signal termination cascade? (5)
- Common drugs to block B1aR pathway?
- DAG; PIP3; cAMP
1. ) Agonist binds 2.) By binds GRK which phosphorylates receptor 3.) this attracts B arrestin 4.) Clatherin helps endocytosis 5.) Either degraded or phosphotases cleave phosphates and B-arrestin leaves - B blockers = Inhibit NE
- Phosphodiesterase to convert cAMP to AMP and not activate PKA
- Ser/Thr Protein Kinases:
- Phosphate group added where?
- Mechanism of the rxn?
- Other forms of post-trans mod? (4)
- ATP: 2 bonds? How many phosphate groups? Roles? (6)
- Hydroxyl of Ser/Thr/Tyr
- OH nu- attack gamma phosphate of ATP
- Acetylation, methylation, glycolcylation, ubiquitination
- phosphoanhydride bonds; 3
- energy equivalent; phosphate donor; nuceotide; converts to cAMP, neuromodulator
- Ser/Thr Protein Kinases:
- How are kinases classified:
- 1? Ex? (3)
- 2? Ex? (2) Problem?
- 3? Ex? (4)
- 4? Ex? (2)
- Protein kinase structure? ATP binds where? Interacts with? What puts ATP in correct location? Which is slow step? Fast? Is active conserved motif? Inactive? Implications?
1.) Phosphorylated Residue: Ser/Thr/Tyr
2.) Substrate Protein: Myosin light chain kinase, EF2 –> many have multiple substrates
3.) Activating stimulus: MAPk
Receptor = Insulin; 2nd messenger = PKA; cyclins = CDK
4.) Phylogenic relationship = ACG; TK
- 1 small lobe and 1 big lobe; cleft b/n the 2; big lobe; Gly rich residues of small lobe; Open=active (allows exchange of ADP for new ATP); Closed = inactive (put y-phos in right place; Almost all; no; target for drugs to distort ATP binding
