A phosphoinositide kinase specific for the D-3 position of the inositol ring, phosphatidylinositol (PI) 3-kinase, associates with activated receptors for platelet-derived growth factor, insulin, and colony-stimulating factor 1, with products of the oncogenes src, fms, yes, crk, and with polyomavirus middle T antigen. Efficient fibroblast transformation by proteins of the abl and src oncogene fa...

PI3Ks (phosphoinositide 3-kinases) regulate many critical cellular responses by producing PI(3,4,5)P(3) (phosphatidylinositol 3,4,5-trisphosphate). To facilitate the spatio-temporal characterization of PI(3,4,5)P(3) in living primary cells, we generated a novel strain of transgenic mice [AktPH (Akt pleckstrin homology domain)-GFP (green fluorescent protein) Tg (transgenic) mice] that express a ...

Cell polarity is crucial for directed migration. Here we show that phosphoinositide 3-kinase (PI(3)K) mediates neutrophil migration in vivo by differentially regulating cell protrusion and polarity. The dynamics of PI(3)K products PI(3,4,5)P(3)-PI(3,4)P(2) during neutrophil migration were visualized in living zebrafish, revealing that PI(3)K activation at the leading edge is critical for neutro...

Phosphatidylinositol (PI) 3-kinase is activated by a variety of agents, including various growth factors, and has been proposed to play a role in initiation of cell growth, proliferation, and differentiation. We here investigate the effect of various membrane lipids on PI 3-kinase immunopurified from human SH-SY5Y neuroblastoma cells. CDP-diacylglycerol (CDP-DAG) inhibited PI 3-kinase activity ...

About 10 years ago there was a heated debate over whether v-Src and several other retrovirally encoded protein-tyrosine kinases had lipid kinase activity in addition to protein kinase activity. Ultimately, the analysis of the unusual lipid kinase activity associated with v-Src led to the discovery of a novel type of phosphatidylinositol (PI) kinase, the PI 3-kinases. This in turn led to the cha...

Phosphatidylinositide (PI) 3-kinase binds to tyrosyl-phosphorylated insulin receptor substrate-1 (IRS-1) in insulin-treated adipocytes, and this step plays a central role in the regulated movement of the glucose transporter, GLUT4, from intracellular vesicles to the cell surface. PDGF, which also activates PI 3-kinase in adipocytes, has no significant effect on GLUT4 trafficking in these cells....

Activation of the collagen receptor glycoprotein VI (GPVI) by a collagen-related peptide (CRP) induces stimulation of platelets and megakaryocytes through the phosphatidylinositol (PI) 3-kinase–dependent pathway leading to activation of Bruton tyrosine kinase (Btk) and phospholipase Cg2 (PLCg2). Here, we present evidence that both proteins undergo PI 3-kinase–dependent translocation to the plas...

OBJECTIVE Contraction of cardiac myocytes is initiated by Ca(2+) entry through the voltage-dependent L-type Ca(2+) channel (LTCC). Previous studies have shown that phosphatidylinositol (PI) 3-kinase signaling modulates LTCC function. Because PI 3-kinases are key mediators of insulin action, we investigated whether LTCC function is affected in diabetic animals due to reduced PI 3-kinase signalin...

Macropinocytosis is a highly conserved endocytic process by which extracellular fluid and solutes are internalized into cells. Macropinocytosis starts with the formation of membrane ruffles at the plasma membrane and ends with their closure. The transient and sequential emergence of phosphoinositides PI(3,4,5)P3 and PI(3,4)P2 in the membrane ruffles is essential for macropinocytosis. By making ...

Classical cadherin adhesion molecules can function as adhesion-activated cell-signaling receptors. One key target for cadherin signaling is the lipid kinase phosphoinositide (PI) 3-kinase, which is recruited to cell-cell contacts and activated by E-cadherin. In this study, we sought to identify upstream factors necessary for E-cadherin to activate PI 3-kinase signaling. We found that inhibition...