| Column 1 | Column 2 (memorize)
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| What evidence demonstrats that NGF is a neurotrophin for sympathetic and some types of sensory neurons, derived from the target tissue? |
- Anti-NGF Ab leads to loss of sympathetic neurons
- Neurons that die during development survive in the presence of NGF
- NGF is expressed in the target tissue of sympathetic and some types of sensory neurons
- NGF overexpression in skin leads to increased number of sympathetic neurons
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| What are the classes of neurotrophin receptors? |
- Trk receptor family
- p75 receptor (low affinity) - binds all neurotrophins. Not understood what it does.
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| Explain the development of the R7 photoreceptor in the ommatidium of the Drosophila compound eye. | It depends on Boss expression by R8. The signaling pathway is: Boss (ligand) → Sevenless (receptor) → SOS → dRas1.
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| Explain the activation mechanism for NGF / TrkA. | NGFs induces dimerization and trans phosphorylation of TrkA. It provides docking sites for PTD and SH2 domain-containing proteins.
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| What are the pathways of TrkA (just give representative)? | Shc, PLCγ, and the "?" pathway (p85/p110 of PI3K).
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| Give the Shc intracellular pathway of TrkA. | SHC → Grb2 → SOS → Ras → Raf → MEK → (MAPK → pp90RSK : serine/threonine kinases)
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| Give the PLCγ intracelluar pathway of TrkA. | Dehydrolysis of PIP2 into DAG and IP3. IP3 → incr. intracellular Ca2+. DAG + Ca2+ → PKC
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| Give the "?" intracelluar pathway of TrkA. | ? → p85 / p110(of PI3K). PI3 Kinase phosphorylates PIP2 into PIP3. PIP3 activates Akt (serine/threonine kinase).
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| CNTF intracellular pathway | CNTF binds CNTF receptor. This leads to the recruitment of gp130/JAK, which recruits LIFRβ/JAK, and JAK is activated. Upon its activation JAK phosphorylates residues on gp130 and LIFRβ. Phosphorylated residues in LIFRβ constitute docking sites for SH2 domain of STAT3. JAK phosphorylates and activates STAT3 and activated STAT3 is translocated to the nucleus.
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| GDNF signals | Each GDNF member binds its a preferred GFRα subunit. All GFRα receptors are GPI-anchored to lipid raft domains of the plasma membrane and are associated with the RET tyrosine kinase. The latter is multimerized and recruits a number of different signaling molecules.
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| What are 3 possible signaling molecules recruited by the RET tyrosine kinase of GDNF signals? |
- Src (non-receptor tyrosine kinase) has its own targets
- Ret + GRB2, Sos, Ras, Raf → MEK → MAPK
- Ret + Shc, GRB2, PI3K → Akt
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| TGFβ signaling | TGFβ receptor consists of two distinct dimers: type 1 dimer and type 2 dimer, which are serine/threonine kinases. Initially, TGFβ binds to the type 2 dimer and type 1 dimer is then recruited to the complex. Constitutively active type 2 dimer phosphorylates type 1 to be catalytically active. Type 1 dimer phosphorylates Smad2, which is then translocated into the nucleus.
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| Which GDNF member binds to what GFRα subunit? | GDNF binds GFRα1, Neurturin (NRTN) binds GFRα2, Artemin (ARTN) binds GFRα3 and Persephin (PSPN) binds GFRα4
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