Selectivity in overlapping MAP kinase cascades

Somsen O.J.G. ; Siderius M. ; Bauer F.F. ; Snoep J.L. ; Westerhoff H.V. (2002)

Article

Some protein kinases operate in more than one mitogen-activated protein-kinase (MAPK) cascade. We here address the question whether specificity of the cascades necessitates physical sequestration of these "promiscuous" kinases (e.g. by binding to scaffolds). A model is constructed, in which two MAPK cascades depend on a single MAP-kinase kinase that is not sequestered in two subpopulations. We show that in this model selective signal transduction is possible provided that there is an additional interaction at the MAP-kinase level, there is no simultaneous activation of more than one response by either signal. We discuss a number of additional interactions that can generate the selectivity, as well as some kinetic features by which this mechanism may be recognized experimentally. © 2002 Elsevier Science Ltd. All rights reserved.

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