Premium
MUC1 (CD227) interacts with lck tyrosine kinase in Jurkat lymphoma cells and normal T cells
Author(s) -
Mukherjee P.,
Tinder T. L.,
Basu G. D.,
Gendler S. J.
Publication year - 2005
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0604333
Subject(s) - jurkat cells , biology , zap70 , microbiology and biotechnology , t cell , t cell receptor , signal transduction , muc1 , tyrosine phosphorylation , tyrosine kinase , cancer research , mucin , immune system , immunology , biochemistry
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 beendetected 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, p56 lck . 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 Ca 2+ 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.