Tranduction Regulation of Transcription

14 grb2 protein also contains an sh3 domain which

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Grb2 protein also contains an SH3 domain, which binds proline-rich domains in proteins like Sos Sos is a GEF for Ras Ras is monomeric G-protein tethered to plasma membrane by lipid tail Localized binding of Grb2-Sos puts Ras-GEF (Sos) in close proximity to Ras-GDP Recruitment of adaptor molecules to phosphorylated RTK 15
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Sos binding to Ras-GDP induces GDP-GTP exchange Ras-GTP is active form Binds to and activates downstream effectors at the plasma membrane GEF activates Ras 16
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Active Ras Triggers Kinase/Phosphorylation Sequence MAP- Mitogen Activated Protein/ Microtubule-Associated Protein 17
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Active MAPK enters nucleus Phosphorylates Transcription factors TF bind to specific response elements in target genes Increases transcription of specific genes Active MAPK enters nucleus and phosphorylates target transcription factors 18
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Normal setting Sevenless receptor is expressed in receiving cell Bride-of-seveless ligand is expressed in signaling cell Binding of Boss to Sev induces signal transduction that results in fate decision = R7 neuron Mutant setting Loss of Sev Receptor leads to change in fate decision = cone cell Genetics to define signal transduction pathway 19
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Mutant setting Loss of Sev Receptor leads to change in fate decision = cone cell Rescue experiments Add molecules (mutant or overexpression of wild type molecules) in mutant cells and determine which ones restore the normal trait (R7 neuron) Epistasis analyses can reveal the order of signaling components Double mutant Analysis Activated Ras restores R7 neuron fate in sev mutant cells Ras is downstream of sev receptor 20
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Regulated by protein cleavage or destruction 21
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22 Wnt Signaling Players Receptors - Frizzled (7-TM spanning) LRP Ligands- Wnts (lipid modified) Intracellular Effectors - Positive Regulators: Dishevelled Beta-catenin TCF (TF) Negative Regulators: Axin (Scaffold) APC (Adaptor) GSK3 (Kinase) TCF (TF) Wnt1 overexpressing breast cancer Wingless fly mutant
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No ligand Destruction complex binds to and targets beta-catenin for destruction Axin acts as scaffold for APC and GSK3
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14 Grb2 protein also contains an SH3 domain which binds...

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