The hormone progesterone stimulates maturation of oocytes inthe toad Xenopus laevis by binding to its receptor. Althoughreceptor number and affinity for the hormone stay relativelyconstant, the dose of hormone required to stimulate meioticmaturation varies according to the environmental stimuli towhich the animal is exposed, but little is known about how thisis regulated. Justman et al. (see the Perspective bySkotheim) combined experimental analysis and mathematical modelingto explore the role of glycogen synthase kinase-3βin desensitization, and a natural, sensitizing costimulus,the amino acid L-leucine. The results help to explain the layeredcomplexity seen in signal transduction networks: If multiplestimuli act upon components of linked feedback loops, cellscan tune their sensitivities dynamically to match their environment.
Q. A. Justman, Z. Serber, J. E. Ferrell Jr., H. El-Samad, K. M. Shokat, Tuning the activation threshold of a kinase network by nested feedback loops. Science 324, 509–512 (2009). [Abstract] [Full Text]