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(1,3)-Fucosyltransferase VII-Dependent Synthesis of P- and E-Selectin Ligands on Cultured T Lymphoblasts1



*
Department of Pathology and
Howard Hughes Medical Research Institute, University of Michigan, Ann Arbor, MI 48109
T lymphocytes up-regulate the synthesis of ligands for E- and
P-selectin during proliferative responses in vivo and in vitro.
Previous studies from our laboratories indicated that the
(1,3)-fucosyltransferase FucT-VII regulates the synthesis of
E-selectin ligands and sialylated Lewisx-related epitopes
(sLex-related epitopes) in human T lymphoblasts. The
current report shows that production of both P- and E-selectin ligands
is FucT-VII dependent, but peak synthesis of each occurs at different
levels of fucosyltransferase activity in intact cells. In brief,
FucT-VII mRNA levels were higher in cultured T lymphoblasts expressing
sLex-related epitopes and both selectin ligands than in
cells expressing P-selectin ligands alone. However, synthesis of the
epitopes and both selectin ligands required the FucT-VII enzyme in
transfected Molt-4 cells. In contrast, neither constitutive nor
transfection-enhanced levels of the FucT-IV enzyme generated active
P-selectin ligands in these lines. In addition, targeted deletion of
the FucT-VII gene in mice markedly inhibited the synthesis of both P-
and E-selectin ligands during blast transformation in vitro. Finally,
the optimal synthesis of active P-selectin ligands occurred at lower
level of FucT-VII activity than required for synthesis of equally
active E-selectin ligands in both cultured T lymphoblasts and FucT-VII
transfectants. Consequently, the FucT-VII enzyme is essential for the
synthesis of both P- and E-selectin ligands by T lymphoblasts, and its
activity determines whether P-selectin ligands are expressed alone or
in conjunction with E-selectin ligands and sLex-related
epitopes on human T cells.
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