H-Ras and phosphoinositide 3-kinase cooperate to induce α(1,3)-fucosyltransferase VII expression in Jurkat T cells

Dimitrios G. Zisoulis, Geoffrey S. Kansas*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

The α(1,3)-fucosyltransferase FucT-VII is essential for the biosynthesis of selectin ligands, but the signaling pathways mediating FucT-VII induction in T cells and other lymphocytes are poorly understood. We have shown previously that sustained activation of Ras in Jurkat T cells induces FucT-VII transcription, which requires the Raf-MEK-ERK pathway. In this study we report that FucT-VII induction is specific to the H-Ras isoform. Jurkat T cells retrovirally transduced with constitutively active H-Ras but not N- or K-Ras up-regulated expression of FucT-VII. Pharmacological inhibition studies also revealed that phosphoinositide 3-kinase (PI3K) activity is required for H-Ras-mediated FucT-VII induction. However, the ability of H-Ras to selectively induce FucT-VII is not a function of the inability of the N- or K-Ras isoforms to activate Raf or PI3K pathways. The use of effector-loop domain mutants of H-Ras, which are impaired for their ability to interact selectively with individual effectors alone or in combination with active Raf, indicated that induction of FucT-VII requires the concomitant activation of at least three signaling pathways. These studies show that H-Ras mediates FucT-VII induction in Jurkat T cells via the activation of the Raf, PI3K, and a distinct, H-Ras-specific effector signaling pathway.

Original languageEnglish (US)
Pages (from-to)39495-39504
Number of pages10
JournalJournal of Biological Chemistry
Volume279
Issue number38
DOIs
StatePublished - Sep 17 2004

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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