Wu Youjun, Griffin Erik E
Dartmouth College, Hanover, NH, United States.
Dartmouth College, Hanover, NH, United States.
Curr Top Dev Biol. 2017;123:365-397. doi: 10.1016/bs.ctdb.2016.11.001. Epub 2016 Dec 5.
PAR-1/MARK kinases are conserved serine/threonine kinases that are essential regulators of cell polarity. PAR-1/MARK kinases localize and function in opposition to the anterior PAR proteins to control the asymmetric distribution of factors in a wide variety polarized cells. In this review, we discuss the mechanisms that control the localization and activity of PAR-1/MARK kinases, including their antagonistic interactions with the anterior PAR proteins. We focus on the role PAR-1 plays in the asymmetric division of the Caenorhabditis elegans zygote, in the establishment of the anterior/posterior axis in the Drosophila oocyte and in the control of microtubule dynamics in mammalian neurons. In addition to conserved aspects of PAR-1 biology, we highlight the unique ways in which PAR-1 acts in these distinct cell types to orchestrate their polarization. Finally, we review the connections between disruptions in PAR-1/MARK function and Alzheimer's disease and cancer.
PAR-1/MARK激酶是保守的丝氨酸/苏氨酸激酶，是细胞极性的重要调节因子。PAR-1/MARK激酶定位于细胞并发挥功能，与前部PAR蛋白相反，以控制多种极化细胞中因子的不对称分布。在本综述中，我们讨论了控制PAR-1/MARK激酶定位和活性的机制，包括它们与前部PAR蛋白的拮抗相互作用。我们重点关注PAR-1在秀丽隐杆线虫受精卵不对称分裂、果蝇卵母细胞前后轴建立以及哺乳动物神经元微管动力学控制中所起的作用。除了PAR-1生物学的保守方面，我们还强调了PAR-1在这些不同细胞类型中发挥作用以协调其极化的独特方式。最后，我们综述了PAR-1/MARK功能破坏与阿尔茨海默病和癌症之间的联系。
