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Scaffold Proteins Confer Diverse Regulatory Properties to Protein Kinase Cascades
Author(s) -
Locasale Jason W,
Chakraborty Arup K,
Shaw Andrey
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a264
Subject(s) - scaffold protein , scaffold , function (biology) , computational biology , microbiology and biotechnology , kinase , biology , signal transduction , chemistry , computer science , database
The assembly of multiple signaling proteins into a complex by a scaffold protein guides many cellular decisions. Despite recent advances, the overarching principles that govern scaffold function are not well understood. We carried out a computational study using kinetic Monte Carlo simulations to understand how spatial localization of kinases on a scaffold may regulate signaling under different physiological conditions. Our studies identify regulatory properties of scaffold proteins that allow them to both amplify and attenuate incoming signals in different biological contexts; these properties are not due to the well‐established prozone or combinatorial inhibition effect. These results bring coherence to seemingly paradoxical observations, and suggest that cells have evolved design rules that enable scaffold proteins to regulate widely disparate cellular functions.