a Sorbonne Universités, UPMC Univ Paris 06, CNRS, Biologie du développement - Institut de Biologie Paris Seine (LBD - IBPS) , Paris , France.
Cell Cycle. 2017 Aug 3;16(15):1440-1452. doi: 10.1080/15384101.2017.1338985. Epub 2017 Jul 19.
The small protein ARPP19 plays a dual role during oocyte meiosis resumption. In Xenopus, ARPP19 phosphorylation at S109 by PKA is necessary for maintaining oocytes arrested in prophase of the first meiotic division. Progesterone downregulates PKA, leading to the dephosphorylation of ARPP19 at S109. This initiates a transduction pathway ending with the activation of the universal inducer of M-phase, the kinase Cdk1. This last step depends on ARPP19 phosphorylation at S67 by the kinase Greatwall. Hence, phosphorylated by PKA at S109, ARPP19 restrains Cdk1 activation while when phosphorylated by Greatwall at S67, ARPP19 becomes an inducer of Cdk1 activation. Here, we investigate the functional interplay between S109 and S67-phosphorylations of ARPP19. We show that both PKA and Gwl phosphorylate ARPP19 independently of each other and that Cdk1 is not directly involved in regulating the biological activity of ARPP19. We also show that the phosphorylation of ARPP19 at S67 that activates Cdk1, is dominant over the inhibitory S109 phosphorylation. Therefore our results highlight the importance of timely synchronizing ARPP19 phosphorylations at S109 and S67 to fully activate Cdk1.
小分子蛋白 ARPP19 在卵母细胞减数分裂恢复过程中发挥双重作用。在非洲爪蟾中，PKA 对 S109 的 ARPP19 磷酸化对于维持处于第一次减数分裂前期的卵母细胞停滞是必需的。孕酮下调 PKA，导致 ARPP19 在 S109 处去磷酸化。这启动了一个信号转导途径，最终导致有丝分裂的普遍诱导物激酶 Cdk1 的激活。最后这一步取决于激酶 Greatwall 对 S67 的 ARPP19 磷酸化。因此，ARPP19 被 PKA 在 S109 处磷酸化，从而抑制 Cdk1 的激活，而当被 Greatwall 在 S67 处磷酸化时，ARPP19 成为 Cdk1 激活的诱导物。在这里，我们研究了 ARPP19 的 S109 和 S67 磷酸化之间的功能相互作用。我们表明 PKA 和 Gwl 可以独立地对 ARPP19 进行磷酸化，并且 Cdk1 不直接参与调节 ARPP19 的生物学活性。我们还表明，激活 Cdk1 的 S67 磷酸化 ARPP19 比抑制性的 S109 磷酸化更占优势。因此，我们的结果强调了及时同步 ARPP19 在 S109 和 S67 处的磷酸化以充分激活 Cdk1 的重要性。
