Department of Genetics, The University of MD Anderson Cancer Center, Houston, Texas, United States of America.
PLoS One. 2009 Oct 14;4(10):e7450. doi: 10.1371/journal.pone.0007450.
The germinal center kinases (GCK) constitute a large, highly conserved family of proteins that has been implicated in a wide variety of cellular processes including cell growth and proliferation, polarity, migration, and stress responses. Although diverse, these functions have been attributed to an evolutionarily conserved role for GCKs in the activation of ERK, JNK, and p38 MAP kinase pathways. In addition, multiple GCKs from different species promote apoptotic cell death. In contrast to these paradigms, we found that a C. elegans GCK, GCK-1, functions to inhibit MAP kinase activation and apoptosis in the C. elegans germline. In the absence of GCK-1, a specific MAP kinase isoform is ectopically activated and oocytes undergo abnormal development. Moreover, GCK-1- deficient animals display a significant increase in germ cell death. Our results suggest that individual germinal center kinases act in mechanistically distinct ways and that these functions are likely to depend on organ- and developmental-specific contexts.
生殖中心激酶 (GCK) 构成了一个庞大而高度保守的蛋白质家族，其涉及多种细胞过程，包括细胞生长和增殖、极性、迁移和应激反应。尽管功能多样，但这些功能归因于 GCK 在激活 ERK、JNK 和 p38 MAP 激酶途径中的进化保守作用。此外，来自不同物种的多种 GCK 促进细胞凋亡。与这些范例相反，我们发现秀丽隐杆线虫的一种 GCK，GCK-1，在秀丽隐杆线虫生殖系中抑制 MAP 激酶的激活和细胞凋亡。在缺乏 GCK-1 的情况下，特定的 MAP 激酶同工型被异位激活，卵母细胞发生异常发育。此外，GCK-1 缺陷动物的生殖细胞死亡明显增加。我们的结果表明，单个生殖中心激酶以不同的机制发挥作用，这些功能可能取决于器官和发育特异性的背景。
