Design of versatile biochemical switches that respond to amplitude, duration, and spatial cues

Azi Lipshtat, Gomathi Jayaraman, John Cijiang He, Ravi Iyengar

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


Cells often mount ultrasensitive (switch-like) responses to stimuli. The design principles underlying many switches are not known.We computationally studied the switching behavior of GTPases, and found that this first-order kinetic system can show ultrasensitivity. Analytical solutions indicate that ultrasensitive first-order reactions can yield switches that respond to signal amplitude or duration. The three-component GTPase system is analogous to the physical fermion gas. This analogy allows for an analytical understanding of the functional capabilities of first-order ultrasensitive systems. Experiments show amplitude- and time-dependent Rap GTPase switching in response to Cannabinoid-1 receptor signal. This first-order switch arises from relative reaction rates and the concentrations ratios of the activator and deactivator of Rap. First-order ultrasensitivity is applicable to many systems where threshold for transition between states is dependent on the duration, amplitude, or location of a distal signal. We conclude that the emergence of ultrasensitivity from coupled first-order reactions provides a versatile mechanism for the design of biochemical switches.

Original languageEnglish
Pages (from-to)1247-1252
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number3
StatePublished - 19 Jan 2010


  • GTpase
  • Signaling
  • Ultrasensitivity


Dive into the research topics of 'Design of versatile biochemical switches that respond to amplitude, duration, and spatial cues'. Together they form a unique fingerprint.

Cite this