SignalingLectureFinal

From the states and weights probability of the

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From the states and weights: Probability of the protein being in the active state, if it is not phosphorylated Probability of the protein being in the active state, if it is phosphorylated The change in activity due to phosphorylation:
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phosphorylation: two internal state variables In the toy model in the figure, => -increase in activity upon phosphorylation In the cell, the increase in activity upon phosphorylation spans from factors of 2 to 1000.
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Eukaryotic signal transduction A more precise realization of the implementation of signaling. We begin with an example that is simple both conceptually and mathematically, namely, prokaryotic two-component signal transduction..
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Two-Component Signal Transduction Next few slides are courtesy of Michael Laub (MIT) and Mark Goulian (Upenn) – experts in the quantitative dissection of signaling networks. This figure shows the generic features of the two-component signal transduction systems.
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SprE OmpR EnvZ PhoB PhoR CusR CusS QseB QseC YedW YedV YfJR YfhK BasR BasS PhoP PhoQ CpxR CpxA CheY UvrY BarA HydG HydD BaeR BaeS FimZ animation by Mark Gouilan Coordinating multiple signaling systems in a single cell
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Phosphotransfer profiling (use complete set of purified RRs) HK + ATP* HK~P* + ADP - RR1 RR2 RR44 ......... RR3 incubate, separate by SDS-PAGE HK~P* + RR HK + RR~P* HK~P RR~P
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Assessing Specificity: Phosphotransfer Profiling +PhoB C. crescentus PhoR profile 60 min phosphotransfer reactions histidine kinases exhibit a strong kinetic preference in vitro for their in vivo cognate substrate specificity based on molecular recognition C. crescentus PhoR profile 5 min phosphotransfer reactions +PhoB
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Signal integration Once we finish with our concrete example of chemotaxis, we will turn to the way in which cells decide where to put new actin filament and that will make us face this question of signal integration.
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G-protein coupled receptors as an example
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