Scaffold-Mediated Organization of Signal Transduction Networks

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Title: Scaffold-Mediated Organization of Signal Transduction Networks
Author: Bumeister, Ronald
Abstract: The Raf -MEK -ERK kinase cascade is a highly conserved signal transduction module involved in cellular processes ranging from proliferation and differentiation to transformation and apoptosis , and is engaged in response to growth factors , cytokines , morphogens , and other extracellular stimuli . Given the ubiquitous nature of this signaling pathway , it is not clear how specialization with respect to various Raf -dependent phenomena is acquired . In theory , functional specificity could be achieved by selectively coupling the core enzymatic components of a cascade to other regulatory pathways depending on the cellular context . Here , by using loss -of -function and partial loss -of -function mutant analysis , we demonstrate that Raf can participate in cell regulatory processes independently of its ability to activate MEK . We also show that scaffolding proteins can serve as specificity determinants in Ras /MAPK signaling , and may function to coordinate the activity of this cascade with additional regulatory pathways required for an appropriate biological response . Thus , we provide evidence for functional diversification both at the level of Raf substrates and at the level of molecular organization by accessory scaffolding molecules .
URI: http : / /hdl .handle .net /2152 .5 /325
Date: 2004-08-19

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Scaffold-Mediated Organization of Signal Transduction Networks. Graduate School of Biomedical Sciences. Available electronically from http : / /hdl .handle .net /2152 .5 /325 .

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