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41 Cards in this Set
- Front
- Back
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NO pathway: what is the effector that causes muscle relaxation?
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Protein Kinase G
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How does NO synthase work?
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NO Synthase is activated by Calmodulin
NO synthase takes arginine and oxygen and converts it to citruline and NO |
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No pathway start --> end
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1. AcetylCholine is the ligand that activates GPCR
2. Activated G protein (GTP) acitvates PLC 3. PLC cleaves membrane phospholipid --> DAG & IP3 4. IP3 increases cytosolic Ca++ levels 5. Ca++ activates Calmodulin 6. Calmodulin activates NO Synthase 7. NO is produced, diffuses from Epiphelial cell to sm. muscle 8. NO activates cytosolic NO receptor which then converts GTP --cGMP 9. cGMP activates Protein Kinase G (PKG) which causes (Phosphorylates) relaxation of smooth muscle |
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Ligands for RTKs
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soluble or membrane bound peptide or protein hormones
NGF, FGF: Fibrogen Growth Factor EGF: Epidermal Growth Factor PDGF insulin |
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What is HER2?
Where is it overexpressed? |
HER2 is a Receptor tyrosine kinases
HER2 over expression is found in breast cancer |
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How are RTKs downregulated
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endocytosis
dephosphorylation |
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General Activation of RTK
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ligand binds receptor
causes dimerization & Trans phosphorylation of lip Tyrosines Phosphorylation of additional Tyrosines that are now binding sites for cytosolic proteins |
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Ligand-induced dimerization of HER1
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Epidermal Growth Factor is the ligand that activates HER1
Causes loops of subunits to interact --> forms homodimer |
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Which HERs can Homodimerize?
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HER1 only
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Which HER is not a kinase?
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HER3
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Which HER can't bind ligand directly?
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HER2
is in a preactivated state dimerizes w/ HER1, HER3, & HER4 |
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RTK signal transduction proteins bind what on RTK?
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Phosphorylated Tyrosines
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What are 2 commonly conserved domains in signal transduction proteins of the RTK initiated pathway?
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SH2 - found in GRB2
PTB |
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GRB2 conserved domains, what do they bind?
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SH2-binds HER's P-Tyrosines
SH3 binds Sos' proline rich binding sites |
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what is Ras, & when is it active?
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Ras is an intracellular GTPase switch
It is active when bound to GTP |
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Walk through of Ras activation pathway
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1. EGF binds HER
2. HER dimerizes & phosphorylates lip Tyrosines 3. GRB2 (with SH2 & SH3 domains) binds HER & Sos 4. Sos now activates Ras by causing it to bind GTP |
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how does Ras activate MAP kinase?
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RRMM
Ras --> Raf --> MEK --> MAP |
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in the Ras--> MAP which use ATP to phosphorylate & activate their targets?
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Raf
MEK MAP |
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what does MEK Phosphorylate
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Activates MAP kinase by Phosphorylating 2 AA of lip
Tyrosine, then Threonine which promotes Kinase activity & dimerization |
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what & where are the targets for MAP kinase in the promotion of c-fos gene?
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activates p90-RSK in the cytosol
TCF: Ternary Complex Factor in nucleus, MAP Phosphorylates a Serine of TCF |
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What must MAP kinase be to enter the nucleous?
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Homo-Dimer
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what & where does p90-RSK do?
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Uses ATP to Phosphorylate SRF (Serum Response Factor) in nucleus
SRF is a Transcription Factor |
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walk through how MAP kinase activates the enhancer, SER (Serum Response Element), of c-fos gene
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1. MAP Kinase Phosphorylates p90-RSK in cytosol
2. MAP Kinase Phosphorylates (dimer does 2) TCF in nucleus p90-RSK Phosphorylates SRF in nucleus 3. TCF & 2 SRFs bind an enhancer region of DNA called SER, which promotes c-fos |
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what is c-fos?
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an early gene for mitosis
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Do yeast contain Receptor Tyrosine Kinases?
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No
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Ste20
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binds cdc42, which is anchored to PM
Ser/Thr kinase Phosphorylates Ste11 |
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Ste11
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binds Ste5 scaffold protein
Ser/Thr kinase analogous to Raf |
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Ste7
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binds Ste5 scaffold protein
Dual specificity: Theronine & Tyrosine MEK |
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Fus3
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(inactive) bound to Ste5 scaffold
after Fus3 is phosphorylated it goes to nucleus & phosphorylates Dig1 & Dig2, relieving their inhibition of Ste12 similar to MAP kinase |
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Walk through the mating pathway in yeast
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1. ligand activates GPCR
2. G-alpha binds GTP & dissociates 3. G-beta/gamma bind Ste-5 scaffold protein 4. Kinase Phosphorylation cascade Ste20--> Ste11 --> Ste7 --> Fus3 5. Fus3 then dissociates & goes to nucleus to Phosphorylate (Inactivate) Dig1 & Dig2 which dissociate from Ste12 6. Ste12 is now able to bind DNA & promote transcription of mating genes |
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what's the short of Osmoregulatory pathway?
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High osmolarity activates a kinase cascade --> --> phosphorylating (activates) Transcription Factor Hot1 which promotes transcription of Osmoresponsive Genes
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what Kinases are in both Mating & Osmoregulatory pathways ?
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Ste20
Ste11 |
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what are the membrane proteins in the Osmoregulatory pathway?
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Sho1 & Msb1
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What is the scaffold protein in the Osmoregulatory pathway?
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Pbs2 is the scaffold protein
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Pbs2
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scaffold protein in Osmoregulatory pathway
binds active Sho1 membrane protein contains MEK Threonine/Tyrosine dual spec kinase that phosphorylates Hog1 binds Ste11 & Hog1 kinases |
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walk through the Osmoregulatory pathway
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1. High osmotic pressure activates membrane proteins Sho1 & Mab1
2. Pbs2 scaffold protein binds Sho1 3. Kinase cascade Ste20 --> Ste11--> Pbs2's integral MEK --> Hog1 4. Hog1 translocates to nucleus & phosphorylates Hot1 transcription factor 5. Hot1 increases transcription of osmoresponsive genes |
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What is CREB?
Where is it Found? |
cAMP Response Element Binding protein
it is a transcription factor that binds DNA segment CRE CREB is only found in the nucleus |
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who activates CREB?
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Protein Kinase A (PKA)
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what is needed in addition to CREB to increase translation?
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CBP/P300
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walk me through the CREB pathway
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PKA translocates into the nucleus & phosphorylates CREB using ATP
2 CREBs bind DNA at CRE & associate w/ CBP/P300 --> promotes transcription of enzymes that convert pyruvate back to glucose |
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not a real card
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not a real card
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