CFM 2: Signal Transduction

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  1. Nitric Oxide mechanism
    In vascular smooth muscle, NO binds to guanylyl cyclase, increasing cGMP, which mediates vasodilation
  2. Nitroglycerin is used to treat _____
  3. Phosphodiesterase type 5
    • Breaks down cGMP
    • PDE5 inhibitors include Viagra, Levitra, Cialis
  4. Why should you not take Viagra while on nitroglycerin?
    • Nitroglycerin is converted to NO, which stimulates cGMP production
    • PDE5 inhibitors like Viagra inhibit enzyme that breaks down cGMP
    • So, too much cGMP
  5. CCR5
    • GPCR that is important for eliminating foreign agents, but is also a receptor that HIV can bind to in order to infect a cell
    • Double-edged sword
  6. SMADs
    Molecules that are phosphorylated and activated by serine/threonine kinase receptors (like TGFβ receptor); they oligomerize when activated and act as transcription factors
  7. TGFβ receptor and disease
    • TGFβ mediates fibrosis (too much TGFβ = fibrosis)
    • TGFβ is anti proliferative and as such acts as a tumor suppressor; downstream SMADs are deleted in numerous cancers
  8. SH2 domains
    • Proteins with SH2 domains (conserved, non catalytic domain) are recruited to receptor tyrosine kinases
    • Biological outcome is related to the combination of SH2 domain containing proteins recruited
  9. Cytokine receptors
    Receptor does not have kinase activity itself, but Jak kinase associated with receptor gets phosphorylated
  10. Ras activation by receptor tyrosine kinase
    • EGF binds receptor, receptor phosphorylates
    • Recruits GRB2, which has SH2 domain (which is recruited by receptor) and SH3 domain (which associates with Sos), but no catalytic domain
    • Now that Sos is recruited, Sos is activated, which then activates Ras, which activates Raf, which starts cascade to activate MAP kinase
Card Set
CFM 2: Signal Transduction
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