A Little Lyn Goes a Long Way: Results of an Experimental/Theoretical Collaboration
Tuesday, October 13, 1998 - 11:00am - 12:00pm
Carla Wofsy (University of New Mexico)
In order to initiate cellular responses to external signaling molecules, receptors of the immune system must aggregate and must interact with specific intracellular enzymes. I will present the results of an experimental/theoretical collaboration regarding one such interaction, that of the enzyme Lyn, a Src family kinase, with the receptor that mediates a class of allergic reactions. Comparison of the predictions of alternative mathematical models (coupled nonlinear ODEs) with measurements of phosphorylation of tyrosine on receptor subunits, in a variety of experiments, reveals that (1) cellular Lyn is compartmentalized, with only a limited supply of the enzyme available to the receptor, (2) compartmentalization is not determined by the domain of Lyn that associates with the plasma membrane, (3) Lyn shuttles among receptors, and aggregation of the receptors leads to extensive redistribution of the available Lyn, and (4) although aggregation of the receptor is essential for signal transduction, aggregation of Lyn is not required. I will touch on the problem that modelers must confront in trying to encompass a more extensive portion of the signaling cascade.