Publication Date:
2008-03-15
Description:
Scaffold proteins link signaling molecules into linear pathways by physically assembling them into complexes. Scaffolds may also have a higher-order role as signal-processing hubs, serving as the target of feedback loops that optimize signaling amplitude and timing. We demonstrate that the Ste5 scaffold protein can be used as a platform to systematically reshape output of the yeast mating MAP kinase pathway. We constructed synthetic positive- and negative-feedback loops by dynamically regulating recruitment of pathway modulators to an artificial binding site on Ste5. These engineered circuits yielded diverse behaviors: ultrasensitive dose response, accelerated or delayed response times, and tunable adaptation. Protein scaffolds provide a flexible platform for reprogramming cellular responses and could be exploited to engineer cells with novel therapeutic and biotechnological functions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bashor, Caleb J -- Helman, Noah C -- Yan, Shude -- Lim, Wendell A -- New York, N.Y. -- Science. 2008 Mar 14;319(5869):1539-43. doi: 10.1126/science.1151153.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Pharmacology, University of California at San Francisco, 600 16th Street, San Francisco, CA 94158, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18339942" target="_blank"〉PubMed〈/a〉
Keywords:
Adaptation, Physiological
;
Adaptor Proteins, Signal Transducing/chemistry/*metabolism
;
Binding Sites
;
*Feedback, Physiological
;
Intracellular Signaling Peptides and Proteins/*metabolism
;
Leucine Zippers
;
MAP Kinase Kinase Kinases/metabolism
;
*MAP Kinase Signaling System
;
Mitogen-Activated Protein Kinases/metabolism
;
Promoter Regions, Genetic
;
Protein Precursors/metabolism/pharmacology
;
Protein Tyrosine Phosphatases/metabolism
;
Recombinant Fusion Proteins/metabolism
;
Saccharomyces cerevisiae/genetics/*metabolism
;
Saccharomyces cerevisiae Proteins/chemistry/*metabolism/pharmacology
;
Systems Biology/methods
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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