The Journal of Immunology, Vol 159, Issue 12 5984-5992, Copyright © 1997 by American Association of Immunologists

ARTICLES

Exploiting the difference between intrinsic and extrinsic kinases: implications for regulation of signaling by immunoreceptors

C Wofsy, C Torigoe, UM Kent, H Metzger and B Goldstein
Department of Mathematics and Statistics, University of New Mexico, Albuquerque 87131, USA.

When receptors must interact with an extrinsic kinase to initiate signaling, the kinase can play a regulatory role that is not available to intrinsic receptor kinases. Whether control is exercised at this level depends critically on the amount of kinase available to the receptors and on the potential for redistribution of the kinase during signaling. This study demonstrates that the high affinity receptor for IgE (Fc epsilonRI) on rat basophilic leukemia cells is regulated by its initiating kinase. We present a mathematical model that allows for the reversible recruitment of extrinsic kinases to phosphorylated immunoreceptor tyrosine-based activation motifs. By comparing model predictions to experimental time courses of phosphorylation, we infer that Lyn is limiting, that redistribution occurs after receptors are aggregated, and that the redistribution makes the relationship between tyrosine phosphorylation and receptor aggregation nonlinear.

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