Signaling cascades: a hidden feedback is revealed

ALEJANDRA C VENTURA; JACQUES-A. SEPULCHRE; SOFIA D MERAJVER

San Jose, USA

Conferencia; The Joint Annual Meetings of the Society for Mathematical Biology and the Japanese Society for Mathematical Biology; 2007

Society for Mathematical Biology

Covalent modification cycles are one of the major intracellular signaling mechanisms. In them, a protein is activated by the addition of a phosphate group and inactivated by the removal of this phosphate. Signaling occurs through networks of these units, even more, several signaling pathways are constituted by a chain or cascade of cycles. The understanding of such cascades has been the subject of a great number of studies. Models in the literature are mostly modular; the description of a single unit is incorporated phenomenologically into a chain of units. Starting from a mechanistic description of a cascade composed by an arbitrary number of cycles, we have derived for the first time a consistent approximation under which that cascade is described with one variable per cycle. The newly derived approximation is not slightly different from previous models, it involves qualitatively different dynamics that we explore and characterize numerically.