Scaffold proteins confer diverse regulatory properties to protein kinase cascades

Jason W. Locasale, Andrey S. Shaw, Arup K. Chakraborty

Research output: Contribution to journalArticlepeer-review

61 Scopus citations


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.

Original languageEnglish
Pages (from-to)13307-13312
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number33
StatePublished - 14 Aug 2007
Externally publishedYes


  • Cell signaling
  • MAPK
  • Mathematical modeling
  • Monte Carlo simulations
  • Phosphatase activity


Dive into the research topics of 'Scaffold proteins confer diverse regulatory properties to protein kinase cascades'. Together they form a unique fingerprint.

Cite this