癌基因与磷脂酰肌醇代谢

Oncogenes and phosphatidylinositol turnover.

作者信息

Cantley L C, Whitman M, Chahwala S, Fleischman L, Kaplan D R, Schaffhausen B S, Roberts T M

出版信息

Ann N Y Acad Sci. 1986;488:481-90. doi: 10.1111/j.1749-6632.1986.tb46580.x.

DOI:10.1111/j.1749-6632.1986.tb46580.x

Abstract

Products of phosphatidylinositol turnover have recently been implicated as regulators of cell growth and differentiation. Transformation of cells in culture by infection with certain viruses (Rous sarcoma virus, Kirsten sarcoma virus, and polyoma virus) or by transfection with the oncogenes carried by these viruses affect the steady-state level of intermediates in the PI turnover pathway. In addition, immunoprecipitates of the transforming gene products of Rous sarcoma virus and polyoma virus contain activities of certain enzymes in the PI turnover pathway. We have previously reported that polyoma middle T immunoprecipitates can catalyze phosphorylation of PI to phosphatidylinositol-4-phosphate (PIP). This activity is not intrinsic to middle T or c-src but is due to a cellular enzyme that specifically associates with this complex. The PI kinase is found in immunoprecipitates of the middle T protein from polyoma viruses that are capable of cell transformation but does not associate with mutants of middle T defective in transformation suggesting that this association may be important for transformation.

摘要

磷脂酰肌醇代谢产物最近被认为是细胞生长和分化的调节因子。通过感染某些病毒（劳氏肉瘤病毒、柯斯顿肉瘤病毒和多瘤病毒）或转染这些病毒携带的癌基因来转化培养中的细胞，会影响磷脂酰肌醇（PI）代谢途径中中间体的稳态水平。此外，劳氏肉瘤病毒和多瘤病毒转化基因产物的免疫沉淀物含有PI代谢途径中某些酶的活性。我们之前报道过，多瘤病毒中T抗原免疫沉淀物可以催化PI磷酸化为磷脂酰肌醇-4-磷酸（PIP）。这种活性并非中T抗原或c-src所固有，而是由于一种与该复合物特异性结合的细胞酶。PI激酶存在于能够进行细胞转化的多瘤病毒中T蛋白的免疫沉淀物中，但不与转化缺陷的中T抗原突变体结合，这表明这种结合可能对转化很重要。