Papazyan Romeo, Doche Michael, Waldron Richard T, Rozengurt Enrique, Moyer Mary Pat, Rey Osvaldo
Unit of Signal Transduction and Gastrointestinal Cancer, Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, 90095-1786, USA.
Exp Cell Res. 2008 Oct 1;314(16):3057-68. doi: 10.1016/j.yexcr.2008.07.014. Epub 2008 Jul 26.
The protein kinase D (PKD) family consists of three serine/threonine protein kinases involved in the regulation of fundamental biological processes in response to their activation and intracellular redistribution. Although a substantial amount of information is available describing the mechanisms regulating the activation and intracellular distribution of the PKD isozymes during interphase, nothing is known of their activation status, localization and role during mitosis. The results presented in this study indicate that during mitosis, PKD3 and PKD are phosphorylated at Ser(731) and Ser(744) within their activation loop by a mechanism that requires protein kinase C. Mitosis-associated PKD3 Ser(731) and PKD Ser(744) phosphorylation is related to the catalytic activation of these kinases as evidenced by in vivo phosphorylation of histone deacetylase 5, a substrate of PKD and PKD3. Activation loop-phosphorylated PKD3 and PKD, as well as PKD2, associate with centrosomes, spindles and midbody suggesting that these activated kinases establish dynamic interactions with the mitotic apparatus. Thus, this study reveals a connection between the PKD isozymes and cell division, suggesting a novel role for this family of serine/threonine kinases.
蛋白激酶D（PKD）家族由三种丝氨酸/苏氨酸蛋白激酶组成，它们参与调节基本生物学过程以响应其激活和细胞内重新分布。尽管已有大量信息描述了在间期调节PKD同工酶激活和细胞内分布的机制，但对于它们在有丝分裂期间的激活状态、定位和作用却一无所知。本研究给出的结果表明，在有丝分裂期间，PKD3和PKD在其激活环内的Ser(731)和Ser(744)位点被磷酸化，这一机制需要蛋白激酶C。有丝分裂相关的PKD3的Ser(731)和PKD的Ser(744)磷酸化与这些激酶的催化激活有关，组蛋白去乙酰化酶5（PKD和PKD3的一个底物）的体内磷酸化证明了这一点。激活环磷酸化的PKD3和PKD以及PKD2与中心体、纺锤体和中间体相关，这表明这些激活的激酶与有丝分裂装置建立了动态相互作用。因此，本研究揭示了PKD同工酶与细胞分裂之间的联系，提示了这个丝氨酸/苏氨酸激酶家族的一种新作用。
