THE PHOSPHATIDYLINOSITOL 3-KINASE-ALPHA IS REQUIRED FOR DNA-SYNTHESIS INDUCED BY SOME, BUT NOT ALL, GROWTH-FACTORS
THE PHOSPHATIDYLINOSITOL 3-KINASE-ALPHA IS REQUIRED FOR DNA-SYNTHESIS INDUCED BY SOME, BUT NOT ALL, GROWTH-FACTORS
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DOI：
10.1073/pnas.91.19.9185
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发表时间：
1994-09-13
影响因子：
11.1
通讯作者：
COURTNEIDGE, SA
中科院分区：
文献类型：
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作者：
ROCHE, S;KOEGL, M;COURTNEIDGE, SA
磷脂酰肌醇3-激酶（PI 3-K）在静止细胞被多种生长因子刺激时被激活。我们已经显微注射抗体的PI 3-K的p110 α亚基到静止的成纤维细胞，并测试其对生长因子的能力，刺激退出从静止和进入S期的影响。这些抗体抑制血小板衍生生长因子诱导的DNA合成，这一结果与先前使用突变型血小板衍生生长因子受体的研究一致。有趣的是，功能性PI 3-K是G（1）的前6小时所必需的-即，直到细胞被定型以产生DNA的时间点之前约4小时。第二种酪氨酸激酶受体，表皮生长因子受体，也需要PI 3-K进行有效的信号传导。然而，集落刺激因子1（其受体与血小板衍生生长因子受体高度相关）可以在没有活性PI 3-K的情况下诱导DNA合成，其受体与G蛋白功能性偶联的两种生长因子（蛙皮素和溶血磷脂酸）也可以诱导DNA合成。因此，这些数据表明，一些，但不是全部，生长因子需要功能性PI 3-K。
The phosphatidylinositol 3-kinase (PI 3-K) becomes activated when quiescent cells are stimulated with a variety of growth factors. We have microinjected antibodies specific for the p110 alpha subunit of the PI 3-K into quiescent fibroblasts and tested their effect on the ability of growth factors to stimulate exit from quiescence and entry into S phase. The antibodies inhibited platelet-derived growth factor-induced DNA synthesis, a result in keeping with previous studies using mutant platelet-derived growth factor receptors. Interestingly, functional PI 3-K was required for the first 6 hr of G(1)-i.e., until approximate to 4 hr before the point at which the cells were committed to make DNA. A second tyrosine kinase receptor, the epidermal growth factor receptor, also required the PI 3-K for efficient signaling. However, colony-stimulating factor 1 (whose receptor is highly related to the platelet-derived growth factor receptor) could induce DNA synthesis in the absence of active PI 3-K, as could two growth factors (bombesin and lysophosphatidic acid) whose receptors are functionally coupled to G proteins. These data, therefore, demonstrate that some, but not all, growth factors require functional PI 3-K.