肝激酶B1和造血干细胞内稳态

Relationship between LKB1 and the homeostasis of hematopoietic stem cell

肝激酶B1(liver kinase B1,LKB1),又名丝氨酸/苏氨酸蛋白激酶11(STK11),是一种蛋白激酶,可磷酸化AMP激活的蛋白激酶和12种其他AMPK相关激酶。LKB1还是一种肿瘤抑制蛋白,生殖细胞LKB1基因突变可引发家族性黑斑息肉综合征,而体细胞突变可造成多种肿瘤发生。小鼠Lkb1的失活可导致造血干细胞(HSC)静息的丧失、快速的HSC消耗、严重的全血细胞减少和最终的致死。Lkb1缺陷的HSC细胞显示出线粒体缺陷、膜电位减少和细胞ATP耗竭。这些结果说明LKB1是一种HSC内稳态和造血过程中的新调节因子。

LKB1（liver kinase B1）,also called STK11（serine/threonine kinase 11）,is a protein kinase which can phosphorylate AMP-activated protein kinase（AMPK） and 12 other AMPK-related kinases.LKB1 is a tumor suppressor,which mutations in germline are associated with the Peutz-Jeghers syndrome and mutations in somatic cell are observed in many kinds of cancers.inactivation of Lkb1 can cause loss of haematopoietic stem cell（HSC） quiescence,rapid HSC depletion,severe pancytopenia and subsequent lethality in mice.Lkb1-deficient HSCs exhibit mitochondrial defects,reduction of mitochondrial membrane potential and depletion of cellular ATP.These results indicate that Lkb1 is a new regulator of HSC homeostasis and haematopoiesis.