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 because of its high affinity association with the v-src oncogene product, pp60v-src and with the polyoma middle t/pp60c-src complex in transformed cells (Sugimoto et al., 1984; Whitman et al., 1985; Whitman et al., 1988). Prior to the discovery of this enzyme, the only phosphorylated forms of phosphatidylinositol known to exist in vivo were phosphatidylinositol-4-phosphate (PtdIns-4-P) and phosphatidylinositol-4,5-bisphosphate (PtdIns-4,5-P2). These lipids are intermediates in the canonical PtdIns Turnover Cycle that leads to the well-known second messengers, inositol-1,4,5-trisphosphate and diacylglycerol (Fig. 1). In vitro, PtdIns 3-Kinase can phosphorylate the D-3 position of PtdIns, PtdIns-4-P or PtdIns-4,5-P2 to produce PtdIns-3-P, PtdIns-3,4-P2 and PtdIns-3,4,5-P3 respectively (Auger et al., 1989; Carpenter and Cantley, 1990)). All three of these lipids have now been detected in mammalian cells (Auger et al., 1989; Stephens et al., 1989). 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 (Lips et al., 1989; Serunian et al., 1989). Rather, they appear to be involved in a distinct regulatory process in the cell.
KeywordsTyrosine Serine Proline Sarcoma Luminal
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