Henry Metzger, NIH
We are analyzing the initial molecular events stimulated by the high-affinity receptor for IgE, FcR I, one of the ``multichain immune response receptors" that play a central role in the initiation and regulation of immune responses. When a multivalent antigen interacts with specific IgE firmly bound to the receptor, the aggregated FcRI initiate a cascade of biochemical events. Considerable experimental data support a molecular mechanism in which the role of aggregation is to stabilize the association of two or more molecules of receptor thereby promoting transphosphorylation of the receptors by a constitutively associated src-family kinase. The tyrosines on the receptor that become phosphorylated then act as docking sites for downstream components of one or more pathways. In this presentation, we review the progress and future challenges for developing a quantitatively accurate description of this system. This work was done jointly with Huaxien Chen, Byron Goldstein , Hana Haleem-Smith, John Inman, Matthew Peorce, Chikako Torigoe, Becky Vonakis, and Carla Wofsy.