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12-02-08 - mammalian cells Regulated Localization Why are...

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Serpentine or G-protein coupled receptors
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AC = adenylate cyclase Gs Gi
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GAP = GTPase activating protein G protein = GTPase GEF = guanine nucleotide exchange factor GDI = guanine dissociation inhibitor
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O OH H H H H O O P O O - N N N N NH 2 cAMP
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Second Messengers Molecules generated by hormonal signals that carry the signal further downstream cyclic nucleotides ions lipids NO, O 2 - , CO (gases) inositol
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Lipids as second messengers: Phosphatidylinositides.
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The ceramide rheostat Ceramide Sphingosine Growth arrest Apoptosis Proliferation
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Serine, C16-CoA Sphingoid base Ceramide Complex Sphingolipids Biosynthesis Catabolism Ethanolamine, C16-al
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SH2, SH3 bind phosphotyrosine residues WW domain binds proline rich sequences Pleckstrin homology binds phosphoinositides PDZ domain binds to S/TxV motif FYVE = phophatidyl inositol Signaling proteins are modular and multivalent
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Signaling proteins are modular and multivalent
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Signaling cascades are modulatory
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Scaffold proteins pre-arrange signaling components
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MAP kinase cascade. Serine/threonine Kinases
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MAP kinase cascades in
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Unformatted text preview: mammalian cells. Regulated Localization Why are signaling pathways so complex? Specificity Signal amplification Adaptability Adaptability Signal bifurcation Adaptability Integration Phosphodiesterases Degrade cGMP and cAMP Turning off signals Phosphatases abrogate kinase signals Phosphatases abrogate inositol polyphosphate signals OH NH 3 + OH R OH NH + O R PLP H B OH NH + O R PLP H+ OH NH + PLP OH NH 3 + Sphingoid base lyase Ion Storage Receptor endocytosis and degradation Liver Muscles +II K M = 0.1mM K M = 10 mM Glucose in blood 4-5 mM So liver does not compete with other tissues F6P turns HKIV off Stimulates liver gluconeogenesis Molecular link between obesity and type II diabetes PPARs Peroxisome proliferator-activated receptors Related to steroid hormone receptors PPAR γ PPAR α = liver Turns on beta oxidation and ketone body formation PPAR δ = liver and muscle Turns on beta oxidation and energy uncoupling...
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