Bio 3105 - Enzyme Coupled Receptors PII.txt

  1. What are the Six Classes of Enzyme-Coupled Receptor?
    • Receptor Tyrosine Kinases
    • Tyrosine Kinase-associated Receptors
    • Receptor-like Tyrosine Phosphatases
    • Receptor Serine/Threonine Kinases
    • Receptor Guanylyl Cyclases
    • Histidine Kinase-Associared Receptors
  2. What is the Basic Structure of a Receptor Tyrosine Kinase?`
    A Cytosolic Kinase Domain and Highly Variable Receptor-Domain outside the Cell.
  3. How does Ligand Binding affect RTK's?
    It activates the Kinase domain.
  4. What is the Drk protein?
    An Protein in R7 development binding to the RTK and Ras-GEF
  5. How does Drk Interact with Ras?
    SH3 Domains (Proline-Rich)
  6. How does Drk interact with the RTK?
    SH2 Domain (Phosphotyrosine)
  7. What is the role of Ras in R7 development?
    To relay the signal
  8. What is the overall effect of BOSS on the R7 cell?
    Regulation of Glucose and Fat Utilization.
  9. What Are Eph receptors?
    A Tyrosine Kinase that guides Cell Migration, Adhesion and Repulsion.
  10. What is an Ephrin?
    A Membrane Bound Ligand for the Eph Receptor
  11. Which Receptor is capable or Bi-Directional Signalling?
    Eph Receptors
  12. How are Ephrins Tethered to the Membrane?
    By a GPI anchor.
  13. How does IRS-1 bind to The Insulin Receptor?
    • Insulin causes Autophosphorylation of it's cytosolic region.
    • The Phosphotyrosine Binding Domain of IRS-1 binds to the Phosphorylated Cytosolic Domain.
  14. What is an Example of a Ras Independant Signalling Pathway?
    The Insulin Pathway
  15. Briefly Describe the Insulin Pathway.
    • Insulin Binds to it's receptor
    • IRS-1 Binds and to the receptor and Phosphorylates Inositol in the Membrane
    • Protein Kinase B Binds to the Phoshpoinositide
    • Protein Kinase B is phosphorylated and Inactivates GSK 3
  16. What is GSK 3? (Insulin pathway)
    A Glycogen Synthase
  17. What is a Cytokine?
    An extracellular signalling protein that acts as a local mediator in cell-to-cell communication
  18. What are Janus Kinases?
    Tyrosine Kinases associated with Cytokine Receptors
  19. What are some ligands for Cytokine Receptors?
    • Hormones (Growth Hormone)
    • Cytokines
  20. What are STAT proteins in the JAK-STAT system?
    • Signal Transducers and Activators of Transcription
    • Latent Gene Regulatory Proteins (Only Migrating to the Nucleus when Activated).
  21. What is the Erythropoietin Receptor's Ligand?
  22. What is the Kinase associated with Erythropoietin signalling?
    JAK2 Kinase
  23. How is the Erythropoietin Receptor (And JAK2) Dephosphorylated (Short Term)?
    • SHP1 Phosphatase binds to phosphotyrosines on the Receptor with it's SH2 domain.
    • The phosphatase Domain then Dephosphorylates the JAK2 Kinase
  24. How is the Erythropoietin Receptor Deactivated (Long Term)?
    • The SOCS Protein SH2 Domain Binds to Phosphotyrosine on the Receptor and JAK Kinase
    • The SOCS-Box Protein Recruits E3 Ubiquitin Ligase
    • Down Regulation Occurs
  25. What is the SOCS Protein?
    • A Protein used in Long-Term receptor down regulation.
    • Attracts E3 Ubiquitin Ligase
  26. Where does the Epo-Receptor go after ubiquitinization?
    To the proteosome to be degraded.
  27. What is Ras?
    A monomeric G-Protein
  28. Where is Ras found?
    • Connected to the plasma membrane
    • Attached via a Farnesyl Lipid Anchor
  29. What is one role of Ras?
    Regulation of Cells into DNA synthesis
  30. What is the effect of injecting Permenantly Active Ras into cells without growth factors?
    Cell will move into S-Phase
  31. What is required for a Cell to move into S-phase?
    • Functional Ras protein
    • Growth factors (PDGF+EGF) to activate Ras
  32. How is Ras coupled to Receptors?
    Through SOS proteins (GEFs) bound to the receptor by GRB2 (Adaptor Proteins)
  33. Starting with Ligand Binding (Receptor). How is Ras activated?
    Ligand binding -> Receptors Dimerize -> Receptor Autophosphorylation -> Binding of GRB2 (SH2 Domain) -> Binding (SH3) & Activation of SOS (GEF) -> Exhange GDP for GTP -> Dissociation of Active Ras
  34. What does MAP stand for?
    Mitogen Activated Kinase
  35. What is a Mitogen?
    An Extracellular Signal Molecule that signals cells to increase rapidly in numbers.
  36. Name the mechanism that Ras uses to Activate MAP.
    A Phosphorylation Cascade
  37. Describe the Phosphorylation Cascade in MAP signalling. Start with the active Ras Protein.
    Active Ras -> Activate MAP Kinase-Kinase-Kinase -> Phosphorylate (Activate) MAP-Kinase-Kinase -> Phosphorylate MAP-Kinase
  38. What are the two potential outcomes of the MAP Phosphorylation Cascade?
    • Changes in Protein Activity
    • Changes in Gene Expression
  39. Where is ATP used in the MAP-Phosporylation Cascade?
    In all phosphorylation steps
  40. What is the main conformational change in activated (Phosphorylated) MAP-Kinase?
    Rotation of the Activation Lip
  41. State one similarity in cell signalling between the Mating Response and Glycerol Synthesis?
    They both undergo a Ras induced Phosphorylation Cascade
  42. How are different signalling pathways kept separate?
    Scaffold Proteins
  43. What does MAP-Kinase do?
    • Relays signals by phosphorylation
    • Moves to Nucleus and Activates Transcriptional factors
  44. What genes does MAP-Kinase activate?
    • Immediate Early Genes
    •  G1 cyclins (cell cycle initiation)
  45. How does MAP-Kinase regulate transcription?
    Activates P90RSK -> Moves into Nucleus -> Activates (Phosphorylates) TCF -> TCF binds to SRE on gene
  46. What is p90rsk?
    • pp90 Ribosome S6 Kinase
    • Activated by MAP-Kinase
    • Activates (Phosphorylates) SRF
    • SRFs bind to SRE region on Gene
  47. TCF is activated by MAP-Kinase. What does TCF stand for?
    Tumor Cytotoxic Factor
  48. How does Ras assist in Plasma membrane docking?
    By activating PI 3-Kinase which phosphorylates inostitol producing docking sites.
  49. How can different Phosphoinositides (and therefore different pathways) be created?
    Using different Kinases
  50. What is the overall function of PI 3-Kinase?
    Activation of siganlling pathways leading to cell growth and survival
  51. Starting with an Activated Receptor B receptor complex, describe the activation of Protein-Kinase C using BTK.
    Activated R-B Complex -> PI-3 Kinase Binding & Activation -> Phosphorylation of Inositol -> BTK & PLC-γ bind to phosphoinositides -> BTK Activates PLC-γ -> PLC-γ cleaves creating IP3 + Diacylglycerol
  52. Starting with a Survival signal describe the pathway leading inhibition of Apoptosis.
    Survival Signal -> Dimerized Autophosporylated RTK -> Activates (Phosphorylates) PI 3-Kinase -> Phosphorylates Inositol -> PDK1 & PKB Bind to Phosphoinosities (PH Domains) -> PDK1 Activates PKB -> Active PKB Dissociates -> PKB Phosphorylates the BAD complex -> Death Inhibitory Protein (BAD) is activated -> Apoptosis is inhibited.
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Bio 3105 - Enzyme Coupled Receptors PII.txt