08MultiEnzymeSystems-EGFsignaling

08MultiEnzymeSystems-EGFsignaling - Basic cell building...

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Basic cell building block + Signal transduction Gumbiner, B., Cell adhesion:The molecular basis of tissue archtecture and morphogenesis, Cell. 84, 345-357 (1996) Materials effects Medium effects
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How Does Receptor Density Affect Subcellular Signaling and Behavior? Sawano, Takayama, Matsuda, Miyawaki Dev. Cell 2002 Local EGF Delivery Local Signaling? Global Signaling? Subcellular Stimulation and Cancer Cancer cells: uncoordinated, moves a lot Cancer cells: often overexpress growth factor receptors (EGF) Iressa: small molecule kinase inhibitor Herceptin: antibody to EGF receptor
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Types of papers Review Paper Nat. Rev. Mol. Cell. 2003 , 4 , 971-974. Original Research • Reynolds, Tischer et al. Nat Cell Biol 2003 , 5, 447-453. Ras Ras signaling signaling Ras is a G-protein GDP bound inactive GTP bound active GEF (guanine nucleotide exchange factor) activates GAP (GTPase activating protein) inactivates Ras Ras Raf MAPK/ERK Signal Signal Genes Genes Ras inactive Ras active GEF GAP
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Raichu - Ras Ras How to sense active Ras? Raf binds active Ras RBD: Ras binding domain of Raf YFP, CFP
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Treatment of Parts of Single Cells Using Laminar Flow Localized EGF Signals in Normal Cell Cell Movemen Sawano, Takayama, Matsuda, Miyawaki Dev. Cell 2002
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What is this movie telling you? What is this movie telling you? About Ras Activation, and why? About EGFR activation, and why? What is the right hand overlay telling you, and why? Ligand -independent Lateral Propagation independent Lateral Propagation of EGF Signals in a Cancer of EGF Signals in a Cancer -like Cell like Cell Sawano, Takayama, Matsuda, Miyawaki Dev. Cell 2002
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Local versus Global Activation of
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08MultiEnzymeSystems-EGFsignaling - Basic cell building...

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