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Type I Phosphatidylinositol Kinase Makes A Novel Inositol Phospholipid, Phosphatidylinositol-3-phosphate

M. Whitman, C. Downes, M. Keeler, T. Keller, L. Cantley
Published 1988 · Biology, Medicine

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The generation of second messengers from the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PtdInsP2) by phospho-inositidase C has been implicated in the mediation of cellular responses to a variety of growth factors and oncogene products1–4. The first step in the production of PtdInsP2 from phosphatidyl-inositol (PtdIns) is catalysed by PtdIns kinase. A PtdIns kinase activity has been found to associate specifically with several oncogene products, as well as with the platelet-derived growth factor (PDGF) receptor5–8. We have previously identified two biochemically distinct PtdIns kinases in fibroblasts, and have found that only one of these, designated type I, specifically associates with activated tyrosine kinases7. We have now characterized the site on the inositol ring phosphorylated by type I PtdIns kinase, and find that this kinase specifically phosphorylates the D-3 ring position to generate a novel phospholipid, phosphatidylinositol-3-phosphate (PtdIns(3)P). In contrast, the main PtdIns kinase in fibroblasts, designated type II, specifically phosphorylates the D-4 position to produce phosphatidylinositol-4-phosphate (PtdIns(4)P), previously considered to be the only form of PtdInsP (ref. 9). We have also tentatively identified PtdIns(3)P as a minor component of total PtdInsP in intact fibroblasts. We propose that type I Ptdlns kinase is responsible for the generation of PtdIns(3)P in intact cells, and that this novel phosphoinositide could be important in the transduction of mitogenic and oncogenic signals.
This paper references
Molecular aspects of cellular regulation
P. Cohen (1980)
Inositol trisphosphates in carbachol-stimulated rat parotid glands.
R. Irvine (1984)
Common elements in growth factor stimulation and oncogenic transformation: 85 kd phosphoprotein and phosphatidylinositol kinase activity
D. Kaplan (1987)
Inositol lipids and cell proliferation.
M. Berridge (1987)
The structures of enzymically produced diphosphoinositide and triphosphoinositide.
C. Prottey (1968)
Specificity of ox brain triphosphoinositide phosphomonoesterase.
M. Chang (1967)
Phosphatidylinositol metabolism and polyoma-mediated transformation.
D. Kaplan (1986)
Association of phosphatidylinositol kinase activity with polyoma middle-T competent for transformation
M. Whitman (1985)
Bovine brain contains two types of phosphatidylinositol kinase.
G. Endemann (1987)
Oncogenes, ions, and phospholipids.
I. Macara (1985)
Gluconeogenesis and related aspects of glycolysis.
H. Hers (1983)
Myo-inositol phosphates obtained by alkaline hydrolysis of beef brain phosphoinositide.
C. Grado (1961)
The structure of triphosphoinositide from beef brain.
D. M. Brown (1966)
Rapid formation of inositol 1,3,4,5-tetrakisphosphate and inositol 1,3,4-trisphosphate in rat parotid glands may both result indirectly from receptor-stimulated release of inositol 1,4,5-trisphosphate from phosphatidylinositol 4,5-bisphosphate.
P. Hawkins (1986)
Evidence for two distinct phosphatidylinositol kinases in fibroblasts. Implications for cellular regulation.
M. Whitman (1987)

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Association of type I phosphatidylinositol kinase activity with mutationally activated forms of human pp60c-src.
T. O. Chan (1990)
Structure and nomenclature of inositol phosphates, phosphoinositides, and glycosylphosphatidylinositols.
P. Murthy (2006)
A screen for phosphatidylinositol 3,4-bisphosphate and other 3-phosphoinositide effector proteins
Miles J Dixon (2010)
Requirement ofPhosphatidylinositol-3
H. Hanafusa (1991)
Studies of a phosphatidylinositol 3-kinase complex linked to vesicular trafficking in human cells.
C. Panaretou (1998)
p53 mutations change phosphatidylinositol acyl chain composition.
Adam Naguib (2015)
New Strategies in Endometrial Cancer: Targeting the PI3K/mTOR Pathway—The Devil Is in the Details
A. Myers (2013)
Phosphoinositide 3‐kinase p110γ in immunity
Carlotta Costa (2011)
Phosphoinositides in cell regulation and membrane dynamics
G. D. Paolo (2006)
Role of PI3K/AKT/mTOR signaling in the cell cycle progression of human prostate cancer.
N. Gao (2003)
The lipid products of phosphoinositide 3-kinase isoforms in cancer and thrombosis
Typhaine Anquetil (2018)
Signals and pathways controlling regulatory T cells
A. Huynh (2014)
Phosphatidylinositol 3-Kinase Activity Is Critical for Glucose Metabolism and Embryo Survival in Murine Blastocysts*
J. Riley (2006)
Involvement of phosphoinositide 3-kinase and its association with pp60src in cholecystokinin-stimulated pancreatic acinar cells.
Fumihiko Nozu (2000)
Signal Transduction in Plant Growth and Development
D. P. Verma (1996)
Accumulation and Storage of Phosphate and Minerals
V. Raboy (1997)
Localization of mRNA for phosphatidylinositol 3-kinase in brain of developing and mature rats.
Y. Ito (1995)
A novel phosphoinositide 3 kinase activity in myeloid-derived cells is activated by G protein βγ subunits
L. Stephens (1994)
Growth Hormone, Interferon-γ, and Leukemia Inhibitory Factor Promoted Tyrosyl Phosphorylation of Insulin Receptor Substrate-1 (*)
L. Argetsinger (1995)
Phosphatidylinositol 3-Kinase, but Not p70/p85 Ribosomal S6 Protein Kinase, Is Required for the Regulation of Phosphoenolpyruvate Carboxykinase (PEPCK) Gene Expression by Insulin
C. Sutherland (1995)
Retroviral oncogenes: a historical primer
P. Vogt (2012)
Hydrogen sulphide induces μ opioid receptor-dependent analgesia in a rodent model of visceral pain
E. Distrutti (2010)
Synthesis of PI(3,4,5)P3 with unsaturated and saturated fatty acid chains
Yutaka Watanabe (1999)
Epidermal Growth Factor Receptor-dependent Akt Activation by Oxidative Stress Enhances Cell Survival*
X. Wang (2000)
Inhibition of adipose differentiation by phosphatidylinositol 3‐kinase inhibitors
X. Xia (1999)
Effect of Huazhuojiedu medicated serum on the proliferation and activation of hepatic stellate cells and the expression of PI3K and p-Akt in rats.
L. Kang (2014)
PI3k and Stat3: Oncogenes that are Required for Gap Junctional, Intercellular Communication
M. Geletu (2019)
The Phosphatidylinositol 3‐Kinase Pathway in Human Malignancies
S. Klempner (2015)
Investigating the Regulation and Function of the NR4A Nuclear Receptors in Cancer
J. A. Beard (2016)
Differences in the metabolism of inositol and phosphoinositides by cultured cells of neuronal and glial origin.
N. Glanville (1989)
Receptor coupling to phosphoinositide signals.
P. Kurian (1992)
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