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cell surface receptors
Cell surface receptors 3 types:
  • Ion channels
  • GPCR
  • Enzyme coupled
    • Enzyme binds - activated catalytic domain or associated enzyme
RTK pathway
RTK pathway Idea: ligand binds to receptor -> tyrosine kinase phos. Tyrosine
  1. GF binding = dimerization & phos. of RTKs (tails)
  2. Proteins (w/ SH2 domains)  bind to phosphorylated tyrosines
  3. Activated proteins relay signal
mitogenic pathway
Mitogenic pathway
  1. Ras-MAP-Kinase
  2. RTK activate Ras -> activate MAP-kinase
    • Cascade leads to  change in enzymes, transcription factor regulation
growth signaling/ survival
Growth Signaling/Survival
  • Pip3-Akt
  1. RTK activate PI-3 -> Akt
    • Akt inhibit apoptosis
  1. Akt activate Tor
    • Inhibit degredation
    • stimulate synthesis (protein)
EGF treatments for cancer
EGF treatments for cancer
Small molecule RTK inhibitor Inhibit phosphorylation? Gefitinib (iressa)     Erlotinib (tarceva) Antibody Bind as ligand, down reg - what is that called? cetuximab  
members of Ras superfamily
Members of Ras superfamily
Ras Cell proliferation Rho Actin assembly Rac Actin polymerization Rab Vesicle targeting Ran Nuclear transport ARF G vesicle coating
growth factors that activate RTks
Growth factors that activate RTKs
EGF (epidermal growth factor) Cancer Insulin Diabetes VEGF (vascular endothelial growth factor) Tumor angiogenesis FGF 1-24 - Fibroblast growth factors Developmental abnormalities PDGF A-D - platelet derived growth factor Wound healing, atherosclerosis
types of cell signaling to each other
  • Types of cell signalling to one another
    1. Endocrine - hormones through blood - specfic, wide distr
    2. Paracrine - around them only - growth factor, prostaglandin
    3. Neuronal - specific kind of paracrine, long distance specific
    4. Contact dependant - closerange, specific - development, immune
small hydrophobic molecules
  • Small hydrophobic = transcription regulators (cortisol, estradiol, testosterone, thyroxine)
  • Ligand -> nuclear receptor protein -> target gene -> expose DNA binding domain and a nuclear localization signal
  • Steriod hormone secreting cell - lipid droplets -> SER -> diffuse out of cell
  • Peptide hormone secreting cell - RER -> G -> granules -> release when signalled
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