Signal Transduction Lecture 1

Principle: signal --> Receptor --> Signal transduction --> Effector Protein --> mod cell function/gene expression
1. Ligand --> receptor --> conformational change
2. Intracell Receptors
3 Paths
1. Endocrine
2. Autocrine
  1. ACh
  2. DA
  3. 5-HTS
  4. NE
  5. Endorphins
3. Paracrine
E.g.:, RECEPTOR TYROSINE KINASE (TK)
1. Encoded by multigene family
  1. 20 human RTK families
3. Pathways
  1. Insulin
    1. CONSERVED: insulin/insulin-like signaling growth factor signaling (IIS)
      1. Growth + dev't
      2. Metabolism
      3. Stress Response
      4. Longevity
      5. uptake ions
      6. Carb, lipid, protein metabolism
        Glu uptake + gluconeogenesis
        Lipogenesis, protein syn, glycogen syn
        Glycolysis
    2. Fun Facts
      1. First hormone isolated/ID'd
      2. Mech not completely known
      3. Getting Insulin
    3. Org Paths
      1. Drosophila
        DILP (drosophila insulin-like peptide)
        8 DILPs + 1 insulin receptor (DInR)
        B-C-A structure conserved
        Homologous to mammalian insulin
        DILP 7: structurally similar to preproinsulin
        Animal dev't + energy homeostasis
      2. C. elegans
        IIS responds to environ. signals
      3. Mammals
4. Family
  1. IR
    1. Mutations
      1. IR resistance; heterozygous = less severe
        normal intrauterine growth; die acidosis at 3-7 days (SO, need IR post-natally only)
      2. 1. Less syn
      3. 2. Inhibit intracell transport
      4. 3. Less affinity to insulin
      5. 4. Inhibit TK
      6. 5. Degrade faster
      7. Donohue Syndrome: IR mutation --> low growth, hypoglycemic, death at 1-2 yrs old, no treatment; chromosome 19
  2. IGF-1R
    1. dysfunction: low intra-uterine + postnatal growth; normal glu
  3. IRR (insulin receptor related receptor): Orphan receptor
5. Domains
  1. Extracell
    1. alpha + 1/3 beta
    2. Ligand binding domain (alpha)
  2. Transmembrane
  3. Intracell
    1. Juxtamembrane
    2. TK domain
      1. Activated by IR conformation change
      2. Transautophosphorylation
    3. C-terminus domain

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Signal Transduction Lecture 1

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