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24 Cards in this Set
- Front
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how phosphorylation regulates Hh pathway
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Gli protein (TF) gets phosphorylated via PKA and is partially proteolyzed ~ if Gli is not proteolyzed, then it will act as a repressor (Gli 3) and bind the target genes |
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how phosphorylation regulates Wnt pathway |
Beta-Catenin gets phosphorylated by Destruction complex which is composed of (APC, Axin, GSK3) ~phosphorylation = tagging for ubiqutination for total degradation |
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core components of Hh pathway |
1. Hh ligands 2. Patched receptor (Ptc) 3. Smoothend (Smo) 4. Gli/Ci proteins (TFs) 5. Protein kinase A (PKA) |
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Hh ligand |
activates Hh pathway by binding to Patched receptor (Ptc) |
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Patched receptor (Ptc) |
12-span transmembrane protein inhibits Smoothend (Smo) when not in the presence of ligand |
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Smoothend (Smo) |
7-alpha-helix transmembrane protein - is inhibited by Patched receptor (Ptc) when no Hh ligand present - is released by Ptc when ligand is present ~ allows activation |
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Gli/Ci proteins (TFs) |
goes into the nucleus to bind or repress target genes depending on the absence or presence of Hh ligand is phosphorylated by PKA for proteolysis |
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Protein Kinase A (PKA) |
phosphorylates Gli for proteolysis |
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explain how proteolysis regulates Hh pathway |
the proteolysis of Gli occurs in the presence of an Hh ligand which prevents Gli from binding the target genes as a repressor in order for the pathway to remain activated |
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explain how proteolysis regulates Wnt pathway |
Beta-catenin is tagged for Ubiquinated degradation via phosphorylation by destruction complex in the absence of Wnt signaling |
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role of cilia |
help localize transduction components of Hh pathway |
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explain the role of Shh-Gli gradient in specifying digit identity in mammals |
Shh levels go from posterior to anterior & and there is a mimicking gradient of Gli activity - in places w/ high levels of Shh there will only be Gli activatiors ~as you move anteriorly, Shh levels decrease so there will be more Gli repressors |
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core components of Wnt pathway |
1. Wnt ligand 2. Beta-Catenin 3. Destruction complex (APC, AXIN, Gsk3) 4. Beta-TrCP 5. PP2A 6. TCF proteins |
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Wnt ligand |
binds some receptor and induces Wnt signal necessary for Wnt pathway activation |
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Beta-Catenin |
regulates target gene expression of Wnt pathway 1. enters nucleus to bind TCF/Lef proteins to turn on target gene expression 2. is phosphorylated by destruction complex via ubiqutinized degradation |
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destruction complex |
composed of three proteins (APC, AXIN, Gsk3) - phosphorylates Beta-Catenin in absence of Wnt signaling - dissociates in the when Wnt signaling is present |
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Beta-TrCP |
enyzme that degrades Beta-Catenin |
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PP2A |
is a phosphatase that removes p-groups from B-Catenin leading to its stabilization |
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TCF proetins |
in the absence of Beta-Catenin, these proteins associate w/ Groucho/Grg co-factors to block target gene expression |
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explain the role of Hh in CNS |
Hh is expressed in Notochord and Floor plate ~decrease in Hh will result in deficient development |
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explain the role of Shh and HPE |
Shh protein haploinsufficiency or other signaling pathway reducing muations can lead to Holoprosencephaly ~this indicates that developing structures likely have different sensitivities to reduced gene dosage |
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Shh protein haploinsufficiency and HPE |
the only phenotype will be brain/face defects |
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Cholesterol depletion and HPE |
DHCR7b encodes an enzyme that is critical in cholesterol synthesis *loss of function alleles in DHCR7b associated w/ Smith-Lemli-Opitz Syndrome & HPE key feature of Smith-Lemli-Opitz Syndrome = HPE |
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role of cholesterol in Hh pathway |
mature Hh originates from self-cleavage action and addition of cholesterol DHCR7 encodes an enzyme critical in cholesterol synthesis ~lack of cholesterol can produce the same types of phenotypes as lack of Shh |