TY - JOUR
T1 - Scaffold proteins confer diverse regulatory properties to protein kinase cascades
AU - Locasale, Jason W.
AU - Shaw, Andrey S.
AU - Chakraborty, Arup K.
PY - 2007/8/14
Y1 - 2007/8/14
N2 - 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 caused by 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.
AB - 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 caused by 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.
KW - Cell signaling
KW - MAPK
KW - Mathematical modeling
KW - Monte Carlo simulations
KW - Phosphatase activity
UR - http://www.scopus.com/inward/record.url?scp=34548059483&partnerID=8YFLogxK
U2 - 10.1073/pnas.0706311104
DO - 10.1073/pnas.0706311104
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C2 - 17686969
AN - SCOPUS:34548059483
SN - 0027-8424
VL - 104
SP - 13307
EP - 13312
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 33
ER -