H-Ras and phosphoinositide 3-kinase cooperate to induce alpha(1,3)-fucosyltransferase VII expression in Jurkat T cells.
The alpha(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.
Zisoulis
Dimitrios G
DG
Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
Kansas
Geoffrey S
GS
D005647:Fucosyltransferases / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006801:Humans; D007536:Isomerism; D019169:Jurkat Cells; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009154:Mutation; D015689:Oncogene Protein p21(ras) / Q000737:chemistry / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D005647:Fucosyltransferases; C031692:galactoside 3-fucosyltransferase; D019869:Phosphatidylinositol 3-Kinases; D019908:Proto-Oncogene Proteins c-raf; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D015689:Oncogene Protein p21(ras)