Auger K R, Serunian L A, Soltoff S P, Libby P, Cantley L C
Department of Cellular and Molecular Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111.
Cell. 1989 Apr 7;57(1):167-75. doi: 10.1016/0092-8674(89)90182-7.
A phosphatidylinositol (PI) kinase activity associated with certain protein tyrosine kinases important in cell proliferation phosphorylates the 3' hydroxyl position of PI to produce phosphatidylinositol-3-phosphate (PI-3-P). Here we report that, in addition to PI-3' kinase activity, anti-phosphotyrosine (alpha-P-tyr) immunoprecipitates from platelet-derived growth factor (PDGF)-stimulated smooth muscle cells (SMC) contain lipid kinase activities that utilize the substrates phosphatidylinositol-4-phosphate (PI-4-P) and phosphatidylinositol-4,5-bisphosphate (PI-4,5-P2). These activities are absent in alpha-P-tyr immunoprecipitates from quiescent SMC. The product of PI-4-P phosphorylation appears to be phosphatidylinositol-3,4-bisphosphate (PI-3,4-P2), a lipid not previously reported. The product of PI-4,5-P2 phosphorylation is phosphatidylinositol-trisphosphate (PIP3). PI-3-P was detected in quiescent SMC and increased only slightly in response to PDGF. PIP3 and the putative PI-3,4-P2 appeared only after the addition of mitogen. Both the temporal production of these novel phospholipids after PDGF stimulation and the observation of the enzymatic activities that produce them in alpha-P-tyr immunoprecipitates suggest that these phospholipids are excellent candidates for mediators of the PDGF mitogenic response.
一种与细胞增殖中某些重要的蛋白酪氨酸激酶相关的磷脂酰肌醇（PI）激酶活性，可使PI的3'羟基磷酸化，生成磷脂酰肌醇-3-磷酸（PI-3-P）。我们在此报告，除了PI-3'激酶活性外，从血小板衍生生长因子（PDGF）刺激的平滑肌细胞（SMC）中免疫沉淀的抗磷酸酪氨酸（α-P-tyr）还含有利用磷脂酰肌醇-4-磷酸（PI-4-P）和磷脂酰肌醇-4,5-二磷酸（PI-4,5-P2）作为底物的脂质激酶活性。这些活性在静止SMC的α-P-tyr免疫沉淀中不存在。PI-4-P磷酸化的产物似乎是磷脂酰肌醇-3,4-二磷酸（PI-3,4-P2），一种以前未报道过的脂质。PI-4,5-P2磷酸化的产物是磷脂酰肌醇三磷酸（PIP3）。PI-3-P在静止SMC中被检测到，并且对PDGF的反应仅略有增加。PIP3和假定的PI-3,4-P2仅在添加促有丝分裂原后出现。PDGF刺激后这些新型磷脂的产生时间以及在α-P-tyr免疫沉淀中产生它们的酶活性的观察表明，这些磷脂是PDGF促有丝分裂反应介质的极佳候选者。
