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Prepublished online as a Blood First Edition Paper on May 8, 2003; DOI 10.1182/blood-2002-11-3551.
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Blood, 1 September 2003, Vol. 102, No. 5, pp. 1771-1778
IMMUNOBIOLOGY
Induction of FucT-VII by the Ras/MAP kinase cascade in Jurkat T cells
Sheila M. Barry,
Dimitrios G. Zisoulis,
Joel W. Neal,
Neil A. Clipstone, and
Geoffrey S. Kansas
From the Department of Microbiology-Immunology, Northwestern University
Medical School, Chicago, IL.
Induction of the 1,3-fucosyltransferase FucT-VII in T lymphocytes is
crucial for selectin ligand formation, but the signaling and transcriptional
pathways that govern FucT-VII expression are unknown. Here, using a novel,
highly phorbol myristate acetate (PMA)responsive variant of the Jurkat
T-cell line, we identify Ras and downstream mitogen-activated protein (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-MEKextracellular signal-regulated kinase (Ras-Raf-MEK-ERK)
pathway in FucT-VII induction by PMA, Ras, and Raf. These studies also
revealed a second, Ras-induced, Raf-1independent pathway that
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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