BIOL300%20Lecture%208%20S.H.

BIOL300%20Lecture%208%20S.H. - How do cells avoid a...

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How do cells avoid a signaling mess? 1) The cell/tissue-specific developmental history ensures that only a subset of these proteins is expressed 2) Scaffold proteins can separate common kinases
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Scaffolds in synthetic biology Bashor CJ et al. (2008), Science 319, 1539, on webCT
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Termination of EGFR signaling (general) 1) phosphatases 2) Receptor endocytosis
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Usually, bulk membrane flow turns over EGFR Upon EGFR activation, the E3 ligase Cbl ubiquitinylates EGFR resulting in endocytosis In contrast to proteasomal degradation, a single ubiquitin is sufficient to induce sorting to the internal membranes of MVBs The EGFR-binding domain alone of Cbl is a dominant-negative oncogenic mutant. It blocks receptor downregulation. Le Roy C and Wrana JLW (2005), Nat Rev Mol Cell Biol 6, 112
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3) Inducible negative regulators of EGFR signaling that ensure paracrine signaling Termination of EGFR signaling (specific) Argos binds to Spi/EGF forming nonfunctional heterodimers Switched on by very high [ligand] Orange = sending cell Green = receiving cell Red = inhibited signaling
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Citri et al. (2006) Nature Reviews Molecular Cell Biology 7 , 505 Medical relevance ERBB=EGFR
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Citri et al. Nature Reviews Molecular Cell Biology 7 , 505 Herceptin antibody induces ERBB2 endocytosis
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BIOL300%20Lecture%208%20S.H. - How do cells avoid a...

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