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Published online before print October 28, 2004
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,1
* Department of Biochemistry and Molecular Biology and
Tumor Biology Program, Mayo Clinic College of Medicine, Mayo Clinic, Scottsdale, Arizona
1 Correspondence: Pinku Mukherjee, Cellular Immunology, and Sandra J. Gendler, Dept. of Biochemistry and Molecular Biology, Tumor Biology Program, Mayo Clinic College of Medicine, 13400 E. Shea Blvd., Scottsdale, AZ 85259. E-mail: mukherjee.pinku{at}mayo.edu and gendler.sandra{at}mayo.edu
MUC1 (CD227) is a large transmembrane epithelial mucin glycoprotein, which is aberrantly overexpressed in most adenocarcinomas and is a target for immune therapy for epithelial tumors. Recently, MUC1 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 MUC1 is not only expressed in these cells but is also phosphorylated upon T cell receptor (TCR) ligation and associates with the Src-related T cell tyrosine kinase, p56lck. Upon TCR-mediated activation of Jurkat cells, MUC1 is found in the low-density membrane fractions, where linker of T cell activation is contained. Abrogation of MUC1 expression in Jurkat cells by MUC1-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 MUC1 in modulating proximal signal transduction events through its interaction with proteins of the activation complex.
Key Words: mucin 1 • p56lck • siRNA • ERK1/2 • calcium flux • T cell activation
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