Disease relevance of dipalmitolyphosphoinositol

• PilT is required for PI(3,4,5)P3-mediated crosstalk between Neisseria gonorrhoeae and epithelial cells [1].

High impact information on dipalmitolyphosphoinositol

• Shallow gradients of chemoattractants, sensed by G protein-linked signaling pathways, elicit localized binding of PH domains specific for PI(3,4,5)P3 at sites on the membrane where rearrangements of the cytoskeleton and pseudopod extension occur [2].
• Engagement of IL3-R and GM-CSF-R in these cells leads to increased and prolonged PI3'K-dependent PI(3,4,5)P3 accumulation and PKB activation [3].
• High osmolarity did not affect phosphatidylinositol 3-kinase activity but led to a marked increase in PI(3,4,5)P3 and a decrease in PI(3,4)P2 formation after pervanadate stimulation, suggesting that hyperosmotic stress has an inhibitory effect on a phosphatidylinositol 5-phosphatase which converts PI(3,4,5)P3 into PI(3,4)P2 [4].
• The PB region of Rac1 showed strong phospholipid interaction with PI(3)P, PI(4)P, PI(5)P, PI(3,4,5)P3, and phosphatidic acid, however, that of Rac2 did not [5].
• Investigations in Dictyostelium discoideum and neutrophils have established that pleckstrin homology (PH) domain-containing proteins that bind to the PI3K products PI(3,4)P2 and PI(3,4,5)P3, such as CRAC (cytosolic regulator of adenylyl cyclase) and Akt/PKB, translocate specifically to the leading edge of chemotaxing cells [6].

Biological context of dipalmitolyphosphoinositol

• Two phases of actin polymerization display different dependencies on PI(3,4,5)P3 accumulation and have unique roles during chemotaxis [7].
• Although PI(3,4,5)P3 and PI(3,4)P2 are known to possibly activate a downstream molecule of PI3-kinase Akt in vitro, overexpression of WT-SHIP2 inhibited insulin-induced phosphorylation and activation of Akt [8].
• AIMS/HYPOTHESIS: SHIP2 is a physiologically important negative regulator of insulin signalling hydrolysing the PI3-kinase product, PI(3,4,5)P3, which also has an impact on insulin resistance [9].
• Exogenous PI(3,4,5)P3 (10 microM), the principal product of IGF-1-stimulated PI3K in 3T3-L1 preadipocytes, had a modest survival effect on its own, reducing cell death from 47.9 +/- 3.4% to 35.6 +/- 3.5% [10].
• Moreover, pretreatment of the control nucleus with PI(3,4,5)P3 alone mimics the anti-apoptotic activity of NGF by selectively preventing apoptosis, for which nuclear Akt is required but not sufficient [11].

Anatomical context of dipalmitolyphosphoinositol

• Here, we clarify the role of SHIP2 possessing 5'-phosphatase activity toward PI(3,4,5)P3 in insulin signalling in the skeletal muscle [8].
• Furthermore, [PI(3,4,5)P3] is translocated to the outer leaflet of the plasma membrane [1].
• Recent studies have shown that certain membrane phospholipids, especially PI(4,5)P2 and PI(3,4,5)P3, regulate actin filament assembly in cells and in cell extracts [12].
• Cell lines lacking both of these enzymatic activities fail to modulate PI(3,4,5)P3 levels, are defective in cytokinesis, and cannot divide in suspension [13].

Associations of dipalmitolyphosphoinositol with other chemical compounds

• Tyrosine phosphorylation of p110 did not alter its catalytic activity, and hydrogen peroxide stimulation did not cause an increase in the intrinsic PI3K activity; however, hydrogen peroxide stimulation did induce PI(3,4,5)P3 accumulation and activate Akt [14].

Gene context of dipalmitolyphosphoinositol

• The pleckstrin homology (PH) domain of ORP3 binds the phosphoinositide-3-kinase (PI3K) products, PI(3,4)P2 and PI(3,4,5)P3 [15].
• While we demonstrate that the Gab-2 PH domain can bind PI(3,4,5)P3, it is dispensable for Gab-2 membrane localisation, tyrosine phosphorylation and signalsome formation [16].
• In chemotaxis, polarity is established by local accumulation of PI(3,4,5)P3 at the cell's leading edge, achieved through temporal and spatial regulation of PI3 kinases and the tumor suppressor, PTEN [13].
• AIMS/HYPOTHESIS: PI(3,4,5)P3 produced by PI3-kinase seems to be a key mediator for insulin's metabolic actions [8].
• B23 mutants that cannot associate with PI(3,4,5)P3 fail to prevent DNA fragmentation, indicating that PI(3,4,5)P3/B23 complex regulates the anti-apoptotic activity of NGF in the nucleus [17].

References