LKB1: cancer, polarity, metabolism, and now fertility.
LKB1: cancer, polarity, metabolism, and now fertility.
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LKB1：癌症、极性、新陈代谢，现在是生育能力。
DOI：
10.1042/bj20082023
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Shaw,ReubenJ
中科院分区：
文献类型：
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作者：
Shaw,ReubenJ
LKB1丝氨酸/苏氨酸激酶是一种肿瘤抑制因子，与遗传性家族性癌症疾病Peutz-Jeghers综合征有关，在很大比例的人类肺癌中处于失活状态。LKB1是一种主激酶，直接磷酸化并激活14个AMPK(AMP激活的蛋白激酶)相关的激酶家族，控制细胞代谢、细胞生长和细胞极性。在这一期的《生物化学杂志》上，Hardie和他的同事们发现了LKB1的一种替代剪接形式，它改变了蛋白质的C末端，其中包含几个已知的翻译后调节位点。短链异构体(LKB1s)虽然广泛表达，但它是在睾丸中表达的唯一剪接异构体，其表达高峰在精子细胞成熟时。缺乏LKB1亚型的雄性小鼠精子严重缺陷，导致不育。
The LKB1 serine/threonine kinase is a tumour suppressor responsible for the inherited familial cancer disorder Peutz-Jeghers syndrome and is inactivated in a large percentage of human lung cancers. LKB1 acts a master kinase, directly phosphorylating and activating a family of 14 AMPK (AMP-activated protein kinase)-related kinases which control cell metabolism, cell growth and cell polarity. In this issue of theBiochemical Journal, Hardie and colleagues discover an alternative splice form of LKB1 that alters the C-terminus of the protein containing a few known sites of post-translational regulation. Although widely expressed, the short isoform (LKB1s) is the sole splice isoform expressed in testes, and its expression peaks at the time of spermatid maturation. Male mice lacking the LKB1sisoform have dramatic defects in spermatozoa, resulting in sterility.