The inflammatory response is characterized by the accumulation of extracellular matrix proteins at sites of injury. Mast cells and basophils accumulate at such inflammatory sites and play a role by releasing an array of mediators. Basophils and mast cells have surface adhesion receptors that are involved in the binding of these cells to other cells or to the extracellular matrix. Such integrin mediated adherence of cells to fibronectin stimulates cell spreading and generates intracellular signals. Previously we observed that the RBL-2H3 cells bind through integrin receptors to surfaces coated with fibronectin; this results in changes in the cytoskeleton, cell spreading and a redistribution of the granules to the periphery of the cells. These changes result in the tyrosine phosphorylation of several proteins including the focal adhesion kinase, pp125FAK (FAK) and in enhanced secretion by the cells. FAK is a widely expressed protein tyrosine kinase that localizes with integrins and several proteins to intracellular sites where cells are in contact with the extracellular matrix. FAK also becomes tyrosine phosphorylated in response to the activation of various receptors including FceRI and antigen receptors on T-cells. In studies during this year we have continued exploring the interaction of intracellular signals generated by adhesion and immune receptor activation.
