LKB1 通过 p114RhoGEF 依赖性 RhoA 激活控制人支气管上皮形态发生。
LKB1 controls human bronchial epithelial morphogenesis through p114RhoGEF-dependent RhoA activation.
机构信息
Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
出版信息
Mol Cell Biol. 2013 Jul;33(14):2671-82. doi: 10.1128/MCB.00154-13. Epub 2013 May 6.
Abstract
LKB1 is a Ser/Thr kinase that plays an important role in controlling both energy metabolism and cell polarity in metazoan organisms. LKB1 is also a tumor suppressor, and homozygous, inactivating mutations are found in a wide range of human cancers. In lung cancer, inactivating mutations are found in 10 to 50% of cases, but the consequences of functional loss in this context are poorly understood. We report here that LKB1 is required for the maturation of apical junctions in the human bronchial epithelial cell line 16HBE14o- (16HBE). This activity is dependent on an interaction with the Rho guanine nucleotide exchange factor p114RhoGEF but is independent of LKB1 kinase activity. Together, LKB1 and p114RhoGEF control RhoA activity in these cells to promote apical junction assembly.
摘要
LKB1 是一种丝氨酸/苏氨酸激酶，在真核生物中对控制能量代谢和细胞极性起着重要作用。LKB1 也是一种肿瘤抑制因子，在广泛的人类癌症中发现其纯合失活突变。在肺癌中，在 10%至 50%的病例中发现失活突变，但在这种情况下功能丧失的后果知之甚少。我们在这里报告，LKB1 是人类支气管上皮细胞系 16HBE14o-（16HBE）中顶端连接成熟所必需的。这种活性依赖于与 Rho 鸟苷酸交换因子 p114RhoGEF 的相互作用，但不依赖于 LKB1 激酶活性。LKB1 和 p114RhoGEF 一起控制这些细胞中的 RhoA 活性，以促进顶端连接的组装。
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Rap2A links intestinal cell polarity to brush border formation.Rap2A 将肠道细胞极性与刷状缘形成联系起来。
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Kinase-independent function of checkpoint kinase 1 (Chk1) in the replication of damaged DNA.有丝分裂检查点激酶 1（Chk1）在损伤 DNA 复制中的激酶非依赖性功能。
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Tumor suppressor function of Liver kinase B1 (Lkb1) is linked to regulation of epithelial integrity.肝激酶 B1（Lkb1）的肿瘤抑制功能与上皮完整性的调节有关。
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The secret life of kinases: functions beyond catalysis.激酶的秘密生活：催化作用之外的功能。
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J Cell Biol. 2011 Oct 17;195(2):245-61. doi: 10.1083/jcb.201104118.
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The role of LKB1 in lung cancer.LKB1 在肺癌中的作用。
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Curr Biol. 2011 Feb 22;21(4):259-69. doi: 10.1016/j.cub.2011.01.010. Epub 2011 Jan 27.
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Spatially restricted activation of RhoA signalling at epithelial junctions by p114RhoGEF drives junction formation and morphogenesis.上皮细胞连接处 RhoA 信号的空间限制激活由 p114RhoGEF 驱动连接形成和形态发生。
Nat Cell Biol. 2011 Feb;13(2):159-66. doi: 10.1038/ncb2156. Epub 2011 Jan 23.
10
The Rho target PRK2 regulates apical junction formation in human bronchial epithelial cells.Rho 靶蛋白 PRK2 调节人支气管上皮细胞顶连接的形成。
Mol Cell Biol. 2011 Jan;31(1):81-91. doi: 10.1128/MCB.01001-10. Epub 2010 Oct 25.
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