MUC1 (CD227) interacts with lck tyrosine kinase in Jurkat lymphoma cells and normal T cells

MUCl (CD227) is a large transmembrane epithetial mucin glycoprotein, which is aberrantly overexpressed in most adenocarcinomas and is a target for immune therapy for epithelial tumors. Recently, MUCI has been detected in a variety of hematopoietic cell malignancies including T and B cell lymphomas and myelomas; however, its function in these cells is not clearly defined. Using the Jurkat T cell lymphoma cell line and normal human T cells, we demonstrate that MUCl is not only expressed in these cells but is also phosphorylated upon T cell receptor (TCR) ligation and associates with the Sre-related T cell tyrosine kinase, p561(lck). Upon TCR-mediated activation of Jurkat cells, MUCI is found in the low-density membrane fractions, where linker of T cell activation is contained. Abrogation of MUCI expression in Jurkat cells by MUCI-specific small interfering RNA resulted in defects in TCR-mediated downstream signaling events associated with T cell activation. These include reduction in Ca2+ influx and extracellular signal-regulated kinase 1/2 phosphorylation, leading to a decrease in CD69 expression, proliferation, and interleukin-2 production. These results suggest a regulatory role of MUCl in modulating proximal signal transduction events through its interaction with proteins of the activation complex.