Phosphatidylinositol-3 kinase dependent pathways: the role in control of cell growth, survival, and malignant transformation.
Phosphatidylinositol-3 kinase dependent pathways: the role in control of cell growth, survival, and malignant transformation.
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发表时间：
2000
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通讯作者：
M. Krasilnikov
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作者：
M. Krasilnikov
磷脂酰肌醇-3激酶（Phosphatidylinositol-3 kinase，PI 3 K）是一种重要的调节蛋白，参与多种信号转导途径，调控细胞的重要功能。PI 3 K的双酶活性（脂质激酶和蛋白激酶）以及该酶激活包括一些癌蛋白在内的许多信号蛋白的能力决定了其在调节细胞功能如生长和存活、衰老和恶性转化中的重要性。PI 3 K的主要效应物是促分裂原转导信号蛋白（蛋白激酶C、磷酸肌醇依赖性激酶、小G蛋白、MAP（促分裂原活化蛋白）激酶），其通过与PI 3 K的脂质产物相互作用或通过蛋白质的PI 3 K依赖性磷酸化而活化。PI 3 K的抗凋亡作用是通过激活来自另一个信号传导途径的蛋白质--蛋白激酶B（PKB）和/或PKB依赖性酶（GSK-3，ILK）来实现的。PI 3 K在恶性转化中起关键作用。PI 3 K本身具有致癌活性，并且还与一些病毒或细胞癌蛋白（src、ras、rac、alb、T抗原）形成复合物，其转化活性仅在PI 3 K存在下实现。PI 3 K的转化作用应该是在细胞信号传导途径的复杂改变的基础上发生的：组成性产生的PI 3 K依赖性有丝分裂原信号的出现和一些原癌基因（src、ras、rac等）的激活，PI 3 K/PKB通路刺激导致细胞凋亡延迟和细胞存活增加，以及肌动蛋白细胞骨架重组。
Phosphatidylinositol-3 kinase (PI3K) is one of the most important regulatory proteins that is involved in different signaling pathways and controlling of key functions of the cell. The double-enzymatic activity of PI3K (lipid kinase and protein kinase) as well as the ability of this enzyme to activate a number of signal proteins including some oncoproteins determines its fundamental significance in regulation of cell functions such as growth and survival, aging, and malignant transformation. Among the main effectors of PI3K are the mitogen-transducing signal proteins (protein kinase C, phosphoinositide-dependent kinases, small G-proteins, MAP (mitogen activated protein) kinases), which are activated either via their interaction with lipid products of PI3K or through PI3K-dependent phosphorylation of proteins. The anti-apoptotic effect of PI3K is realized by activation of proteins from another signaling pathway--protein kinase B (PKB) and/or PKB-dependent enzymes (GSK-3, ILK). PI3K plays a critical role in malignant transformation. PI3K itself possesses oncogenic activity and also forms complexes with some viral or cellular oncoproteins (src, ras, rac, alb, T-antigen), whose transforming activities are realized only in presence of PI3K. The transforming effect of PI3K is supposed to occur on the basis of complex alterations in cellular signaling pathways: appearance of constitutively generated PI3K-dependent mitogen signal and activation of some protooncogenes (src, ras, rac, etc.), PI3K/PKB-pathway stimulation resulting in delay of apoptosis and increase of cell survival, and actin cytoskeleton reorganization.