Visualizing and manipulating phosphoinositide and phospholipid signaling

Published on August 14, 2008 Reviewed on November 22, 2019   55 min

Other Talks in the Category: Methods

0:00
Hello, this is Glenn Prestwich, I'm a professor of medicinal chemistry at the University of Utah, and I'm going to be talking today about the use of chemical probes for visualizing and manipulating phosphoinositide and phospholipid signaling in cells.
0:14
Lipids are important mediators of cellular communication, they can occur both outside the cells in the extracellular medium, or inside cells. The external messengers, such as lysophosphatidic acid are important cell mitogens and control cell migration and proliferation, whereas messengers that are inside the cells, such as the phosphoinositides and other phospholipids on the inner leaflet, recruit proteins and the complexes then end up controlling cell shape, cytoskeletal rearrangements, cell survival, cell differentiation and metabolic events within the cell.
0:47
The poly-phosphoinositides occur in eight chemical forms. There is the phosphatidylinositol itself, with no additional phosphates on the myo-inositol head group attached through a phosphodiester bond to a diacylglycerol moiety, or you can have a single phosphate, as in the phosphomonoesters PI(3)P, PI(4)P and PI(5)P. You can have three different forms of phosphoinositide bisphosphates such as PI(4,5)P2, PI(3,4)P2 and PI(3,5)P2, or a single trisphosphate PI(3,4,5)P3. For additional information on the synthesis of the native phosphoinositides and their affinity probes, and for the uses of these, I would refer the listener to review articles as shown in the bottom of the slide.
1:34
In Salt Lake City we view phosphoinositide signaling in a slightly different way, we view it in three dimensions, where the phosphoinositide energy requiring kinase is using ATP to put additional phosphates onto the phosphoinositide head-group and ultimately getting to Mount Supreme up there. PIP3 is the most highly phosphorylated and most highly interactive phosphoinositide, giving rise to mitogenic effects in cell growth, carcinogenesis, abnormal as well as normal responses in inflammatory and immune response, and in normally controlling the insulin response. In addition to the kinases there are phosphatases which remove phosphate groups, as well as phospholipases. We'll talk more about these and how to manipulate those later on in this talk.
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Visualizing and manipulating phosphoinositide and phospholipid signaling

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