Evidence that SHIP-1 contributes to phosphatidylinositol 3,4,5-trisphosphate metabolism in T lymphocytes and can regulate novel phosphoinositide 3-kinase effectors.
(2002)
Journal - Journal of immunology (Baltimore, Md. : 1950) (United States )
Abstract :
The leukemic T cell line Jurkat is deficient in protein expression of the lipid phosphatases Src homology 2 domain containing inositol polyphosphate phosphatase (SHIP) and phosphatase and tensin homolog deleted on chromosome ten (PTEN). We examined whether the lack of expression of SHIP-1 and PTEN is shared by other leukemic T cell lines and PBLs. Analysis of a range of cell lines and PBLs revealed that unlike Jurkat cells, two other well-characterized T cell lines, namely CEM and MOLT-4 cells, expressed the 5'-phosphatase SHIP at the protein level. However, the 3-phosphatase PTEN was not expressed by CEM or MOLT-4 cells or Jurkat cells. The HUT78 cell line and PBLs expressed both SHIP and PTEN. Jurkat cells exhibited high basal levels of phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P(3); the lipid substrate for both SHIP and PTEN) as well as saturated protein kinase B (PKB) phosphorylation. Lower levels of PI(3,4,5)P(3) and higher levels of phosphatidylinositol 3,4-bisphosphate (PI(3,4)P(2)) as well as unsaturated constitutive phosphorylation of PKB were observed in CEM and MOLT-4 cells compared with Jurkat cells. In PBLs and HUT78 cells which express both PTEN and SHIP-1, there was no constitutive PI(3,4,5)P(3) or PKB phosphorylation, and receptor stimuli were able to elicit robust phosphorylation of PKB. Expression of a constitutively active SHIP-1 protein in Jurkat cells was sufficient to reduce both constitutive PKB membrane localization and PKB phosphorylation. Together, these data indicate important differences between T leukemic cells as well as PBLs, regarding expression of key lipid phosphatases. This study provides the first evidence that SHIP-1 can influence the constitutive levels of PI(3,4,5)P(3) and the activity of downstream phosphoinositide 3-kinase effectors in T lymphocytes.
| ISSN : | 0022-1767 |
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| Mesh Heading : | 1-Phosphatidylinositol 3-Kinase Animals Antibodies, Monoclonal Antigens, CD28 Antigens, CD3 Blood Proteins Cell Membrane Cells, Cultured Enzyme Inhibitors Epitopes, T-Lymphocyte Humans Inositol Phosphates Jurkat Cells Ligands Mice PTEN Phosphohydrolase Phosphatidylinositol Phosphates Phosphatidylinositols Phosphoproteins Phosphoric Monoester Hydrolases Phosphorylation Protein Structure, Tertiary Proto-Oncogene Proteins Proto-Oncogene Proteins c-akt Receptors, Antigen, T-Cell T-Lymphocyte Subsets Tumor Cells, Cultured Tumor Suppressor Proteins Tyrosine antagonists & inhibitors metabolism immunology metabolism immunology metabolism metabolism enzymology pharmacology metabolism physiology biosynthesis metabolism metabolism biosynthesis metabolism drug effects metabolism physiology metabolism biosynthesis metabolism immunology |
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| Mesh Heading Relevant : | Protein-Serine-Threonine Kinases src Homology Domains metabolism metabolism physiology enzymology |
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Evidence That SHIP-1 Contributes to Phosphatidylinositol 3,4,5-Trisphosphate Metabolism in T Lymphocytes and Can Regulate Novel Phosphoinositide 3-Kinase Effectors1
(2002)
Journal - The Journal of Immunology
Abstract :
The leukemic T cell line Jurkat is deficient in protein expression
ofthe lipid phosphatases Src homology 2 domain containing inositol
polyphosphatephosphatase (SHIP) and phosphatase and tensin
homolog deletedon chromosome ten (PTEN). We examined whether the lack
of expressionof SHIP-1 and PTEN is shared by other leukemic T cell
linesand PBLs. Analysis of a range of cell lines and PBLs revealed
thatunlike Jurkat cells, two other well-characterized T cell lines,
namelyCEM and MOLT-4 cells, expressed the 5'-phosphatase SHIP at the
proteinlevel. However, the 3-phosphatase PTEN was not expressed byCEM
or MOLT-4 cells or Jurkat cells. The HUT78 cell line andPBLs expressed
both SHIP and PTEN. Jurkat cells exhibited highbasal levels of
phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3;the
lipid substrate for both SHIP and PTEN) as well as saturatedprotein
kinase B (PKB) phosphorylation. Lower levels of PI(3,4,5)P3
andhigher levels of phosphatidylinositol 3,4-bisphosphate
(PI(3,4)P2)as well as unsaturated constitutive
phosphorylation of PKB wereobserved in CEM and MOLT-4 cells compared
with Jurkat cells.In PBLs and HUT78 cells which express both PTEN and
SHIP-1,there was no constitutive PI(3,4,5)P3 or PKB
phosphorylation,and receptor stimuli were able to elicit robust
phosphorylationof PKB. Expression of a constitutively active SHIP-1
proteinin Jurkat cells was sufficient to reduce both constitutive PKB
membranelocalization and PKB phosphorylation. Together, these data
indicateimportant differences between T leukemic cells as well as
PBLs,regarding expression of key lipid phosphatases. This study
providesthe first evidence that SHIP-1 can influence the constitutive
levelsof PI(3,4,5)P3 and the activity of downstream
phosphoinositide3-kinase effectors in T
lymphocytes.