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

Pinku Mukherjee, T. L. Tinder, G. D. Basu, Sandra J. Gendler

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

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 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.

Original languageEnglish (US)
Pages (from-to)90-99
Number of pages10
JournalJournal of Leukocyte Biology
Volume77
Issue number1
DOIs
StatePublished - Jan 2005

Keywords

  • Calcium flux
  • ERK1/2
  • Mucin 1
  • T cell activation
  • p56
  • siRNA

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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