The kinase inhibitor staurosporine induces G1 arrest at two points: effect on retinoblastoma protein phosphorylation and cyclin-dependent kinase 2 in normal and transformed cells.
The kinase inhibitor staurosporine induces G1 arrest at two points: effect on retinoblastoma protein phosphorylation and cyclin-dependent kinase 2 in normal and transformed cells.
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发表时间：
1994-11
期刊：
影响因子：
11.2
通讯作者：
J. Schnier;D. Gadbois;K. Nishi;E. Bradbury
中科院分区：
文献类型：
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作者：
J. Schnier;D. Gadbois;K. Nishi;E. Bradbury
Staurosporine（ST）是一种蛋白激酶抑制剂，浓度为20 nM时，可将正常二倍体成纤维细胞阻滞3 h进入G1期（H。A. Crissman等人，Proc. Natl. Acad. Sci.美国，88：7580-7584，1991; K. Abe等人，Exp. Cell Res.，192：122-127，1991）。ST（2 nM）诱导一个新的G1阻滞点在6 h进入G1。在2 nM ST阻滞点观察到视网膜母细胞瘤蛋白的部分磷酸化，而在20 nM阻滞点视网膜母细胞瘤蛋白未磷酸化或磷酸化不足。这与细胞周期蛋白依赖性激酶2（CDK 2）的活性和p33 CDK 2的Thr 160残基的磷酸化相关。细胞周期蛋白E和细胞周期蛋白D1/2水平在20 nM ST阻滞点降低。在HeLa细胞，不逮捕在G1响应2或20 nM ST，视网膜母细胞瘤蛋白和CDK 2磷酸化和CDK 2活性不受ST。这些结果表明，ST抑制一个或多个G1调节蛋白激酶，这是上游的CDK 2。
Staurosporine (ST), a protein kinase inhibitor, at a concentration of 20 nM arrests normal diploid fibroblasts 3 h into G1 (H. A. Crissman et al., Proc. Natl. Acad. Sci. USA, 88: 7580-7584, 1991; K. Abe et al., Exp. Cell Res., 192: 122-127, 1991). ST (2 nM) induces a new G1 arrest point at 6 h into G1. Partial phosphorylation of the retinoblastoma protein was observed at the 2 nM ST arrest point, whereas the retinoblastoma protein was unphosphorylated or underphosphorylated at the 20 nM arrest point. This correlated with the activity of the cyclin-dependent kinase 2 (CDK2) and the phosphorylation of the Thr160 residue of p33CDK2. The cyclin E and cyclin D1/2 levels were reduced at the 20 nM ST arrest point. In HeLa cells that do not arrest in G1 in response to 2 or 20 nM ST, the retinoblastoma protein and CDK2 phosphorylations and CDK2 activity were not affected by ST. These results suggest that ST inhibits one or more G1-regulating protein kinases, which lie upstream of CDK2.