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Prepublished online as a Blood First Edition Paper on May 8, 2003; DOI 10.1182/blood-2002-11-3551.

Submitted November 22, 2002
Accepted April 22, 2003
Induction of FucT-VII by the Ras/MAP kinase cascade in Jurkat T cells
Sheila M Barry, Dimitrios G Zisoulis, Joel H Neal, Neil A Clipstone, and Geoffrey S Kansas*
Microbiology-Immunology, Northwestern University Medical School, Chicago, IL, USA
* Corresponding author; email: gsk{at}northwestern.edu.
Induction of the a1,3 fucosyltransferase FucT-VII in T lymphocytes is crucial for selectin ligand formation, but the signaling and transcriptional pathways which govern FucT-VII expression are unknown. Here, using a novel, highly PMA-responsive variant of the Jurkat T cell line, we identify Ras and downstream MAP kinase pathways as essential mediators of FucT-VII gene expression. PMA induced FucT-VII in only a subset of treated cells, similar to expression of FucT-VII in normal activated CD4 T cells. Introduction of constitutively active Ras or Raf by recombinant retroviruses induced FucT-VII expression only in that subset of cells expressing the highest levels of Ras, suggesting that induction of FucT-VII required a critical threshhold of Ras signaling. Both PMA treatment and introduction of active Ras led to rolling on E-selectin. Pharmacologic inhibition studies confirmed the involvement of the classic Ras-Raf-MEK-ERK pathway in FucT-VII induction by PMA, Ras, and Raf. These studies also revealed a second, Ras-induced, Raf1-independent pathway which participated in induction of FucT-VII. Strong activation of Ras represents a major pathway for induction of FucT-VII gene expression in T cells.

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