lecture 3

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Author:
kbroady
ID:
181465
Filename:
lecture 3
Updated:
2012-11-03 19:55:35
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development
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lecture 3
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  1. 6 major signaling families
    • steroids
    • BMP
    • FGF
    • 7 transmembrane / G-coupled pathways
    • Wnt
    • Hedgehog
  2. steroids
    • same molecule is both receptor and TF (because it passes through cell membrane)
    • no amplification or branching
  3. BMPs
    • Bone Morphogenetic Progein Family
    • dimeric molecules (2 subunits; can be homo- and heter- dimers, many combinations possible)
    • transmembrane receptor kinase (enzyme that transfers phosphates)
    • amplification occurs because this is enzymatic
  4. FGF
    • Fibroblast growth factor family
    • transmembrane receptor kinase (transfers phosphates)
    • stimulates cascade (lots of amplification)
  5. 7 transmembrane / G-coupled pathways
    • receptor goes back and forth across membrane 7 times
    • many things can serve as ligands (light, hormones, proteins, etc)
    • G protein is stimulated by ligand binding
  6. Wnt pathway
    • multi-pass transmembrane surface receptor (called frizzled) inhibits kinase activity
    • leads to build up of B-catenin by inhibition of degradation
  7. Hedgehog pathway
    • lipid attaches to signal
    • binds to cells surface receptor called 'patched'
    • double negative circuit - inhibitor is inhibited
    • series of targets is activated
  8. 4 major transcription factor families
    • homeodomains
    • basic helix loop helix (bHLH) proteins
    • Zinc finger proteins
    • HMG (high mobility group) proteins
  9. homeodomain
    • named for homeotic trransformations in flies (hox)
    • one-thing-becoming-another types of transformations
    • recognition helix that sits down in major groove of DNA and interacts with amino acid side chains and bases
  10. bHLH proteins
    • recognition helix sits in groove of DNA
    • 'basic' = positive charge binds to DNA backbone
    • 'HLH' = additional domain that makes dimers (allows for several combinations and thus several targets)
  11. Zinc finger proteins
    • projecting fold binds to DNA via recognition sequences
    • each zinc finger binds 2 or 3 base pairs
    • with more fingers, size of target sequence can be increased
  12. HMG proteins
    • run through agarose gels with high mobility
    • L shaped inserts into DNA helix, inducing bend in DNA molecule
    • bend can bring distant sites which can influence transcription
    • example: SRY
  13. Hirschprung's disease
    • pigmentation changes andĀ enlarged colon (absense of autonomic ganglion cells in intenstine leading to lack of peristalsic contractions of gut)
    • disease of the neural crest
    • problems with cells that have to migrate the furthest (from dorsal neural tube)
    • multiple causes (defect in 7 transmembrane / G coupled pathways; )

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