PROTEIN TYROSINE KINASE‐DEPENDENT REGULATION OF ADENYLATE CYCLASE AND PHOSPHATIDYLINOSITOL 3‐KINASE ACTIVATES THE EXPRESSION OF GLIAL FIBRILLARY ACIDIC PROTEIN UPON INDUCTION OF DIFFERENTIATION IN RAT C6 GLIOMA
PROTEIN TYROSINE KINASE‐DEPENDENT REGULATION OF ADENYLATE CYCLASE AND PHOSPHATIDYLINOSITOL 3‐KINASE ACTIVATES THE EXPRESSION OF GLIAL FIBRILLARY ACIDIC PROTEIN UPON INDUCTION OF DIFFERENTIATION IN RAT C6 GLIOMA
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DOI：
10.1006/cbir.2000.0636
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发表时间：
2001-05
影响因子：
3.9
通讯作者：
D. Roymans;B. Grobben;P. Claes;H. Slegers
中科院分区：
文献类型：
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作者：
D. Roymans;B. Grobben;P. Claes;H. Slegers
胶质纤维酸性蛋白 (GFAP) 在 cAMP 介导的诱导胶质祖细胞分化为 II 型星形胶质细胞时表达。该蛋白受激素、生长因子和细胞因子的调节，但参与调节 GFAP 表达的信号转导途径很大程度上未知。使用特定的蛋白激酶抑制剂来研究其对大鼠C6胶质瘤细胞中GFAP表达的影响。 Herbimycin A 是一种选择性蛋白酪氨酸激酶抑制剂，在 cAMP 类似物或 β-肾上腺素受体介导的分化诱导作用下，可降低 GFAP mRNA 和蛋白表达。后一种抑制剂减弱了腺苷酸环化酶引起的 cAMP 升高，并消除了磷脂酰肌醇 3-激酶 (PI 3-K) 的活性。这些数据表明 GFAP 表达受到蛋白质酪氨酸磷酸化的调节，从而调节 C6 神经胶质瘤细胞中的 cAMP 浓度和 PI 3-K 活性。
Glial fibrillary acidic protein (GFAP) is expressed upon cAMP‐mediated induction of differentiation of glial progenitor cells into type II astrocytes. The protein is regulated by hormones, growth factors and cytokines but the signal transduction pathways involved in the regulation of GFAP expression are largely unknown. Specific protein kinase inhibitors were used to study their effect on the expression of GFAP in rat C6 glioma cells. Herbimycin A, a selective protein tyrosine kinase inhibitor, reduced GFAP mRNA and protein expression upon cAMP analog or β‐adrenergic receptor‐mediated induction of differentiation. The latter inhibitor attenuated the elevation of cAMP by adenylate cyclase and abolished the activity of phosphatidylinositol 3‐kinase (PI 3‐K). These data indicate that GFAP expression is regulated by protein tyrosine phosphorylations, modulating the cAMP concentration and PI 3‐K activity in C6 glioma cells.