A novel phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase associates with the interleukin-3 receptor.

The Journal of Biological Chemistry
L LiuG Krystal

Abstract

To gain insight into the intracellular signaling cascades that are activated by the binding of interleukin-3 (IL-3) to its target cells, we have embarked on the identification of proteins that are associated with the IL-3 receptor (IL-3R). In a previous study we reported that a 110-kDa serine/threonine protein kinase is constitutively associated with the IL-3R and activated following IL-3 stimulation. We now report that a phosphatidylinositol-3,4, 5-trisphosphate (PtdIns-3,4,5-P3) 5-phosphatase (5-ptase) is also constitutively associated with the IL-3R. This 5-ptase is magnesium-dependent and removes the 5-position phosphate from PtdIns-3,4,5-P3 but does not metabolize PtdIns-4,5-P2, inositol (Ins)-1,3,4,5-P4, or Ins-1,4,5-P3. This substrate specificity distinguishes it from any previously characterized 5-ptase. Interestingly, it may be bound indirectly via phosphatidylinositol 3-kinase (PI 3-kinase), another enzyme that is constitutively bound to the IL-3R. However, unlike PI 3-kinase which becomes activated following IL-3 stimulation, this receptor-associated 5-ptase activity does not increase following IL-3 stimulation, and its primary function may be to keep the principal in vivo product of PI 3-kinase, PtdIns-3,4,5-P3, at ...Continue Reading

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Citations

Apr 6, 2004·Developmental and Comparative Immunology·Daniel R BarredaMiodrag Belosevic
Jun 4, 1999·Progress in Biophysics and Molecular Biology·M HuberG Krystal
Oct 23, 1997·Proceedings of the National Academy of Sciences of the United States of America·Z SongyangT F Franke
Mar 31, 1999·Proceedings of the National Academy of Sciences of the United States of America·A D MundayC A Mitchell
Aug 27, 2009·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Roberto J Botelho
Feb 28, 1997·The Journal of Biological Chemistry·A B JeffersonP W Majerus
Jun 22, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·M HuberG Krystal
May 1, 1997·Molecular and Cellular Biology·M Deuter-ReinhardW M Kavanaugh

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