Sewing A, Müller R
Institut für Molekularbiologie und Tumorforschung (IMT), Philipps Universität Marburg, Germany.
Oncogene. 1994 Sep;9(9):2733-6.
Cyclin D1 is a nuclear phosphoprotein that is thought to play a major role in the control of G0/G1-->S progression. The fact that its expression is not tightly regulated during cell cycle progression suggests that its activity might be modulated by post-translational mechanisms. In the present study, we show that out of five serine-threonine kinases tested only protein kinase A (PKA) was able to phosphorylate cyclin D1 in vitro. In agreement with this observation, forskolin treatment, but not TPA stimulation, led to increased phosphorylation of cyclin D1 in vivo. Phosphoamino acid analysis and two-dimensional phosphopeptide mapping of wild-type and truncated cyclin D1 proteins showed that PKA phosphorylates three distinct serine residues in cyclin D1 at positions 90, 197 and 234. Serine-90 is located within the cyclin box, raising the possibility that phosphorylation of cyclin D1 might play a role in regulating the interaction with other proteins.
细胞周期蛋白D1是一种核磷蛋白，被认为在控制G0/G1期向S期的进程中起主要作用。其在细胞周期进程中表达未受到严格调控，这表明其活性可能受翻译后机制调节。在本研究中，我们发现，在所测试的5种丝氨酸 - 苏氨酸激酶中，只有蛋白激酶A（PKA）能够在体外磷酸化细胞周期蛋白D1。与这一观察结果一致，福司可林处理而非佛波酯刺激导致体内细胞周期蛋白D1的磷酸化增加。对野生型和截短型细胞周期蛋白D1蛋白进行的磷酸氨基酸分析和二维磷酸肽图谱分析表明，PKA在细胞周期蛋白D1的90、197和234位磷酸化三个不同的丝氨酸残基。丝氨酸90位于细胞周期蛋白框内，这增加了细胞周期蛋白D1磷酸化可能在调节与其他蛋白相互作用中发挥作用的可能性。
