Phosphorylation of high-mobility group protein A2 by Nek2 kinase during the first meiotic division in mouse spermatocytes
Phosphorylation of high-mobility group protein A2 by Nek2 kinase during the first meiotic division in mouse spermatocytes
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DOI：
10.1091/mbc.e03-09-0638
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发表时间：
2004-03-01
影响因子：
3.3
通讯作者：
Sette, C
中科院分区：
文献类型：
--
作者：
Di Agostino, S;Fedele, M;Sette, C
丝裂原活化蛋白激酶（MAPK）途径是维持两次减数分裂期间染色质浓缩和避免第二轮DNA复制所必需的。然而，MAPK途径在染色质上的分子靶点尚未被确定。在这里，我们表明，建筑染色质蛋白HMGA 2是高度表达的男性减数分裂细胞。此外，Nek 2是一种在小鼠粗线期精母细胞中通过MAPK途径激活的丝氨酸-苏氨酸激酶，在体外和小鼠精母细胞中直接与HMGA 2相互作用。这种相互作用不依赖于Nek 2的活性，似乎是组成性的。在从粗线期到中期的进程中，Nek 2被激活，HMGA 2以MAPK依赖性方式磷酸化。我们还发现Nek 2在体外磷酸化HMGA 2，这种磷酸化降低了HMGA 2对DNA的亲和力，并可能有利于其从染色质中释放。事实上，我们发现大多数HMGA 2与小鼠粗线期精母细胞的染色质相关，而在G2/M期进展时，它被排除在染色质之外。由于hmga 2-/-小鼠是不育的，并且显示出精子发生的显著损伤，因此HMGA 2和Nek 2之间的功能性相互作用可能在减数分裂中染色质凝聚的正确过程中起着至关重要的作用。
The mitogen-activated protein kinase (MAPK) pathway is required for maintaining the chromatin condensed during the two meiotic divisions and to avoid a second round of DNA duplication. However, molecular targets of the MAPK pathway on chromatin have not yet been identified. Here, we show that the architectural chromatin protein HMGA2 is highly expressed in male meiotic cells. Furthermore, Nek2, a serine-threonine kinase activated by the MAPK pathway in mouse pachytene spermatocytes, directly interacts with HMGA2 in vitro and in mouse spermatocytes. The interaction does not depend on the activity of Nek2 and seems constitutive. On progression from pachytene to metaphase, Nek2 is activated and HMGA2 is phosphorylated in an MAPK-dependent manner. We also show that Nek2 phosphorylates in vitro HMGA2 and that this phosphorylation decreases the affinity of HMGA2 for DNA and might favor its release from the chromatin. Indeed, we find that most HMGA2 associates with chromatin in mouse pachytene spermatocytes, whereas it is excluded from the chromatin upon the G2/M progression. Because hmga2-/- mice are sterile and show a dramatic impairment of spermatogenesis, it is possible that the functional interaction between HMGA2 and Nek2 plays a crucial role in the correct process of chromatin condensation in meiosis.