ERK as a model for systems biology of enzyme kinetics in cells

Alan S. Futran, A. James Link, Rony Seger, Stanislav Y. Shvartsman

Research output: Contribution to journalReview article

36 Scopus citations

Abstract

A key step towards a chemical picture of enzyme catalysis was taken in 1913, when Leonor Michaelis and Maud Menten published their studies of sucrose hydrolysis by invertase. Based on a novel experimental design and a mathematical model, their work offered a quantitative view of biochemical kinetics well before the protein nature of enzymes was established and complexes with substrates could be detected. Michaelis-Menten kinetics provides a solid framework for enzyme kinetics in vitro, but what about kinetics in cells, where enzymes can be highly regulated and participate in a multitude of interactions? We discuss this question using the Extracellular Signal Regulated Kinase (ERK), which controls a myriad functions in cells, as a model of an important enzyme for which we have crystal structures, quantitative in vitro assays, and a vast list of binding partners. Despite great progress, we still cannot quantitatively predict how the rates of ERK-dependent reactions respond to genetic and pharmacological perturbations. Achieving this goal, which is important from both fundamental and practical standpoints, requires measuring the rates of enzyme reactions in their native environment and interpreting these measurements using simple but realistic mathematical models - the two elements which served as the cornerstones for Michaelis' and Menten's seminal 1913 paper.

Original languageEnglish (US)
Pages (from-to)R972-R979
JournalCurrent Biology
Volume23
Issue number21
DOIs
StatePublished - Nov 4 2013

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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