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6 major signaling families
- steroids
- BMP
- FGF
- 7 transmembrane / G-coupled pathways
- Wnt
- Hedgehog
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steroids
- same molecule is both receptor and TF (because it passes through cell membrane)
- no amplification or branching
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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
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FGF
- Fibroblast growth factor family
- transmembrane receptor kinase (transfers phosphates)
- stimulates cascade (lots of amplification)
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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
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Wnt pathway
- multi-pass transmembrane surface receptor (called frizzled) inhibits kinase activity
- leads to build up of B-catenin by inhibition of degradation
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Hedgehog pathway
- lipid attaches to signal
- binds to cells surface receptor called 'patched'
- double negative circuit - inhibitor is inhibited
- series of targets is activated
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4 major transcription factor families
- homeodomains
- basic helix loop helix (bHLH) proteins
- Zinc finger proteins
- HMG (high mobility group) proteins
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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
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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)
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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
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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
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Hirschprung's disease
- pigmentation changes and 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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