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

@article{Whitman1988TypeIP,
  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},
  journal={Nature},
  year={1988},
  volume={332},
  pages={644-646}
}
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… 

Role of Phosphatidylinositol 3-Kinase in Growth Factor and Oncogene Signaling

The lipid products of PtdIns 3-Kinase are not substrates for the phospholipases type C and are not intermediates in the canonical PTDIns Turnover Cycle, rather, they appear to be involved in a distinct regulatory process in the cell.

Studies of a phosphatidylinositol 3-kinase complex linked to vesicular trafficking in human cells.

A human homologue of the yeast Vps34p protein, Ptdlns 3-kinase has been identified and shown to form a complex with a protein o f 150kDa (termed p l50), raising the possibility that a human VpsI5p, a 170kDa serine/threonine protein kinase, is also a human.

Phosphatidylinositol 4-kinases and the role of polyphosphoinositides in cellular regulation.

  • L. Pike
  • Biology, Chemistry
    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.

PI 3-Kinase and Receptor-Linked Signal Transduction

Classical phosphoinositide metabolism leading to the well-known second messengers diacylglycerol (DAG) and inositol-1,4,5-trisphosphate (InsP3), was elucidated more than 10 years ago and led to the discovery of the novel PI pathway.

Phosphatidylinositol 3‐kinase

  • R. KapellerL. Cantley
  • Biology, Chemistry
    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.

Phosphoinositides I: Enzymes of Synthesis and Degradation

Current knowledge of PtdIns4K structure, function and regulation is summarized and it is indicated that the enzymes perform non-redundant roles in trafficking and signalling.
...

References

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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.

Oncogenes, ions, and phospholipids.

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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).

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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.

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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.

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.

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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.