Aggregation of many cell surface receptors results in tyrosine phosphorylation of intracellular proteins. The phosphorylation state of these proteins then controls enzymatic activity and protein-protein association or dissociation thereby propagating and regulating downstream signal transduction. The level of protein phosphorylation of a molecule is due to the balance between protein tyrosine kinase and phosphatase activities. Therefore, it is important to understand the role of the protein tyrosine phosphatases in initiating, maintaining and regulating signal transduction in cells. In studies during this last year we found that the SH2 domain containing protein tyrosine phosphatase SHP-1 and SHP- 2 associate with Fc-epsilon-RI and that the SHP-2 also associates with the adhesion molecule PECAM-1 that is tyrosine phosphorylated by activation of different integrin or immune receptors.