Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Mol Cell Biol. 2013 Jul;33(14):2671-82. doi: 10.1128/MCB.00154-13. Epub 2013 May 6.
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.
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。
