SR protein-specific kinase 1 is highly expressed in testis and phosphorylates protamine 1
SR protein-specific kinase 1 is highly expressed in testis and phosphorylates protamine 1
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DOI：
10.1093/nar/27.14.2972
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发表时间：
1999-07-15
影响因子：
14.9
通讯作者：
Giannakouros, T
中科院分区：
文献类型：
--
作者：
Papoutsopoulou, S;Nikolakaki, E;Giannakouros, T
精氨酸/丝氨酸蛋白激酶构成一类新型酶，可以修饰精氨酸/丝氨酸（RS）二肽基序，对于前体mRNA剪接至关重要的SR剪接因子是最具特征的含有RS结构域的蛋白质之一。两种SR蛋白特异性激酶SRPK 1和SRPK 2被认为对这些蛋白的磷酸化具有高度特异性，从而有助于剪接调节。然而，尽管SR蛋白在后生动物中或多或少是保守的，并且具有相当普遍的组织分布，但我们现在证明SRPK 1主要在睾丸中表达，对成年小鼠睾丸横切面原位表达分析表明，SRPK 1 mRNA在所有生殖细胞中都有丰富的表达，但在成熟精子中没有表达，RS激酶活性主要存在于细胞质中，仅在细胞核中检测到最小的活性，在对SRPK 1的睾丸特异性底物的研究中，我们发现该酶磷酸化人鱼精蛋白1以及存在于睾丸中的SR蛋白质的细胞质池，鱼精蛋白1属于小的碱性富含精氨酸的蛋白质家族，其在成熟精子的发育过程中取代组蛋白。这种渐进替换的结果是形成高度紧凑的染色质结构，没有任何转录活性。这些发现表明SRPK 1可能不仅在前mRNA剪接中起作用，而且在精子染色质的凝聚中也起作用。
Arginine/serine protein kinases constitute a novel class of enzymes that can modify arginine/serine (RS) dipeptide motifs, SR splicing factors that are essential for pre-mRNA splicing are among the best characterized proteins that contain RS domains. Two SR protein-specific kinases, SRPK1 and SRPK2, have been considered as highly specific for the phosphorylation of these proteins, thereby contributing to splicing regulation, However, despite the fact that SR proteins are more or less conserved among metazoa and have a rather ubiquitous tissue distribution we now demonstrate that SRPK1 is predominantly expressed in testis, In situ expression analysis on transverse sections of adult mouse testis shows that SRPK1 mRNA is abundant in all germinal cells but not in mature spermatozoa, RS kinase activity was found primarily in the cytosol and only minimal activity was detected in the nucleus, In a search for testis-specific substrates of SRPK1 we found that the enzyme phosphorylates human protamine 1 as well as a cytoplasmic pool of SR proteins present in the testis, Protamine 1 belongs to a family of small basic arginine-rich proteins that replace histones during the development of mature spermatozoa. The result of this progressive replacement is the formation of a highly compact chromatin structure devoid of any transcriptional activity. These findings indicate that SRPK1 may have a role not only in pre-mRNA splicing, but also in the condensation of sperm chromatin.