Type I phosphatidylinositol kinase makes a novel inositol phospholipid, phosphatidylinositol-3-phosphate

  title={Type I phosphatidylinositol kinase makes a novel inositol phospholipid, phosphatidylinositol-3-phosphate},
  author={Malcolm Whitman and C. Peter Downes and Marilyn L. Keeler and Tracy L. Keller and Lewis C. Cantley},
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… Expand
Role of Phosphatidylinositol 3-Kinase in Growth Factor and Oncogene Signaling
Phosphatidylinositol 3-kinase (PtdIns 3-Kinase) is an enzyme that phosphorylates the D-3 position of the inositol ring of the membrane lipid, phosphatidylinositol (PtdIns). It was discovered becauseExpand
Studies of a phosphatidylinositol 3-kinase complex linked to vesicular trafficking in human cells.
Phosphoinositide 3-kinases (PI 3-kinases) are signal transducing molecules that catalyse the addition of phosphate to the 3-OH position of the inositol ring o f phosphoinositides. PI 3-kinase hasExpand
Phosphatidylinositol 4-kinases and the role of polyphosphoinositides in cellular regulation.
  • L. Pike
  • Biology, Medicine
  • Endocrine reviews
  • 1992
The properties of the phosphatidylinositol 4-kinases and the potential role of polyphosphoinositides in the regulation of cellular processes are focused on. Expand
Phosphoinositide 3-kinase: a new effector in signal transduction?
This review brings together recent information on the isolation, characterization and regulation of PI 3-kinase, the cellular occurrence of 3-phosphorylated inositol phospholipids and possible functions of the PI 3 -kinase pathway in cell signalling. Expand
PDGF-dependent tyrosine phosphorylation stimulates production of novel polyphosphoinositides in intact cells
Both the temporal production of these novel phospholipids after PDGF stimulation and the observation of the enzymatic activities that produce them in alpha-P-tyr immunoprecipitates suggest that these phospholIPids are excellent candidates for mediators of the PDGF mitogenic response. Expand
PI 3-Kinase and Receptor-Linked Signal Transduction
Classical phosphoinositide (PI) metabolism leading to the well-known second messengers diacylglycerol (DAG) and inositol-1,4,5-trisphosphate (InsP3), was elucidated more than 10 years ago (Fig.Expand
Phosphatidylinositol 3-kinase: A Novel Signal Transduction Pathway?
The existence of newly described polyphosphoinositides that are responsive to mitogen stimulation or oncogenic transformation in cultured mammalian cells suggests that they are important signaling molecules in the signal transduction pathway for mitogenic protein tyrosine kinases. Expand
Phosphatidylinositol 3‐kinase
  • R. Kapeller, L. Cantley
  • Biology, Medicine
  • BioEssays : news and reviews in molecular, cellular and developmental biology
  • 1994
The homology of the yeast vps34 with the mammalian phosphatidylinositol 3‐kinase has suggested a role for this pathway in vesicular trafficking, and the 3‐phosphoinositide pathway has been implicated in growth factor‐dependent mitogenesis, membrane ruffling and glucose uptake. Expand
Phosphoinositides I: Enzymes of Synthesis and Degradation
Phosphatidylinositol 4-phosphate (PtdIns4P) is a quantitatively minor membrane phospholipid which is the precursor of PtdIns(4,5)P2 in the classical agonist-regulated phospholipase C signallingExpand


Evidence for two distinct phosphatidylinositol kinases in fibroblasts. Implications for cellular regulation.
Comparison of the immunoprecipitated PtdIns kinase with the activities identified by ion-exchange chromatography indicates that it is the Type I enzyme which specifically associates with the middle-T/pp60c-src complex and appears to co-precipitate with partially purified platelet derived growth factor (PDGF) receptor. Expand
Oncogenes, ions, and phospholipids.
  • I. Macara
  • Chemistry, Medicine
  • The American journal of physiology
  • 1985
The model suggests that the early (competence) events in the initiation of cell proliferation are triggered by activation of phosphatidylinositol (PI) turnover, which releases two second messengers, 1,2-diacylglycerol (1, 2-DG) and inositol-1,4,5-trisphosphate (IP3). Expand
Phosphatidylinositol metabolism and polyoma-mediated transformation.
The effect of polyoma middle-sized tumor antigen (MTAg) on phosphatidylinositol metabolism has been characterized in vivo and in vitro using polyoma-transformed and polyoma-infected cells. CellsExpand
Bovine brain contains two types of phosphatidylinositol kinase.
Two phosphatidylinositol (PI) kinases from bovine brain were separated by rate zonal sucrose gradient centrifugation of detergent-solubilized membranes and only one peak of activity is observed which is indistinguishable from brain type 2 PI kinase. Expand
Common elements in growth factor stimulation and oncogenic transformation: 85 kd phosphoprotein and phosphatidylinositol kinase activity
The results suggest that the 85 kd phosphoprotein, a putative PI kinase, is a substrate for both the PDGF receptor and MTAg/pp60c-src tyrosine kinase activities. Expand
Association of phosphatidylinositol kinase activity with polyoma middle-T competent for transformation
The results suggest that viral transformation may be directly connected to a complex network of second messengers generated from PI turnover8–18 and that mutants of middle-T defective in transformation indicate a close correlation between PI kinase activity and transformation. Expand
Myo-inositol phosphates obtained by alkaline hydrolysis of beef brain phosphoinositide.
It is now apparent that the nutritional requirement for myoinositol in many cells is related to its participation as a building unit of myo-inositol-containing phospholipids (phosphoinositides), and it is established that the phosphatidyl group is attached in one of the enantiomorphic l-positions of myO- inositol. Expand
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.
It is suggested that, during carbachol stimulation of parotid slices, the key event in inositol lipid metabolism is the activation of phosphatidylinositol 4,5-bisphosphate-specific phospholipase C. Expand
The structure of triphosphoinositide from beef brain.
The structure has been shown to be the same as that of the triphosphoinositide isolated from beef brain by a method which depends upon the extraction, purification and dissociation of a protein-inositide complex. Expand
Inositol trisphosphates in carbachol-stimulated rat parotid glands.
The most likely structure of this inositol trisphosphate is (D/L)-myo-inositol 1,3,4-trisph phosphate, which yields altritol after periodate treatment followed by reduction and dephosphorylation. Expand