Alien Registration- Serunian, Alice (Portland, Cumberland County)

https://digitalmaine.com/alien_docs/32051/thumbnail.jp

Novel Function of Phosphoinositide 3-Kinase in T Cell Ca\u3csup\u3e2+\u3c/sup\u3e Signaling

This study presents evidence that phosphoinositide (PI) 3-kinase is involved in T cell Ca2+ signaling via a phosphatidylinositol 3,4,5-trisphosphate PI(3,4,5)P3-sensitive Ca2+entry pathway. First, exogenous PI(3,4,5)P3 at concentrations close to its physiological levels induces Ca2+ influx in T cells, whereas PI(3,4)P2, PI(4,5)P2, and PI(3)P have no effect on [Ca2+]i. This Ca2+ entry mechanism is cell type-specific as B cells and a number of cell lines examined do not respond to PI(3,4,5)P3 stimulation. Second, inhibition of PI 3-kinase by wortmannin and by overexpression of the dominant negative inhibitor Δp85 suppresses anti-CD3-induced Ca2+response, which could be reversed by subsequent exposure to PI(3,4,5)P3. Third, PI(3,4,5)P3 is capable of stimulating Ca2+ efflux from Ca2+-loaded plasma membrane vesicles prepared from Jurkat T cells, suggesting that PI(3,4,5)P3 interacts with a Ca2+ entry system directly or via a membrane-bound protein. Fourth, although D-myo-inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P4) mimics PI(3,4,5)P3 in many aspects of biochemical functions such as membrane binding and Ca2+ transport, we raise evidence that Ins(1,3,4,5)P4 does not play a role in anti-CD3- or PI(3,4,5)P3-mediated Ca2+ entry. This PI(3,4,5)P3-stimulated Ca2+ influx connotes physiological significance, considering the pivotal role of PI 3-kinase in the regulation of T cell function. Given that PI 3-kinase and phospholipase C-γ form multifunctional complexes downstream of many receptor signaling pathways, we hypothesize that PI(3,4,5)P3-induced Ca2+ entry acts concertedly with Ins(1,4,5)P3-induced Ca2+ release in initiating T cell Ca2+ signaling. By using a biotinylated analog of PI(3,4,5)P3 as the affinity probe, we have detected several putative PI(3,4,5)P3-binding proteins in T cell plasma membranes

Alien Registration- Serunian, Leon (Saco, York County)

https://digitalmaine.com/alien_docs/3306/thumbnail.jp

Alien Registration- Serunian, Alice (Portland, Cumberland County)

https://digitalmaine.com/alien_docs/32051/thumbnail.jp

Alien Registration- Serunian, Leon (Saco, York County)

https://digitalmaine.com/alien_docs/3306/thumbnail.jp

Alien Registration- Serunian, Hanenn (Portland, Cumberland County)

https://digitalmaine.com/alien_docs/32052/thumbnail.jp