• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文OA文献 >Phosphorylation of the protein kinase mutated in Peutz-Jeghers cancer syndrome, LKB1/STK11, at Ser431 by p90RSK and cAMP-dependent protein kinase, but not its farnesylation at Cys433, is essential for LKB1 to suppress cell growth
【2h】

Phosphorylation of the protein kinase mutated in Peutz-Jeghers cancer syndrome, LKB1/STK11, at Ser431 by p90RSK and cAMP-dependent protein kinase, but not its farnesylation at Cys433, is essential for LKB1 to suppress cell growth

机译：p90 RSK 和cAMP依赖性蛋白激酶使Peutz-Jeghers癌症综合征LKB1 / STK11在Ser431处发生突变的蛋白激酶发生磷酸化，而在Cys 433 处没有发生法呢基化，对于LKB1抑制细胞生长至关重要

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务，本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文，但由于OA文献来源多样且变更频繁，仍可能出现获取不到、文献不完整或与标题不符等情况，如果获取不到我们将提供退款服务。请知悉。
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Peutz-Jeghers syndrome is an inherited cancer syndrome that results in a greatly increased risk of developing tumors in those affected. The causative gene is a protein kinase termed LKB1, predicted to function as a tumor suppressor. The mechanism by which LKB1 is regulated in cells is not known. Here, we demonstrate that stimulation of Rat-2 or embryonic stem cells with activators of ERK1/2 or of cAMP-dependent protein kinase induced phosphorylation of endogenously expressed LKB1 at Ser(431). We present pharmacological and genetic evidence that p90(RSK) mediated this phosphorylation in response to agonists that activate ERK1/2 and that cAMP-dependent protein kinase mediated this phosphorylation in response to agonists that activate adenylate cyclase. Ser(431) of LKB1 lies adjacent to a putative prenylation motif, and we demonstrate that full-length LKB1 expressed in 293 cells was prenylated by addition of a farnesyl group to Cys(433). Our data suggest that phosphorylation of LKB1 at Ser(431) does not affect farnesylation and that farnesylation does not affect phosphorylation at Ser(431). Phosphorylation of LKB1 at Ser(431) did not alter the activity of LKB1 to phosphorylate itself or the tumor suppressor protein p53 or alter the amount of LKB1 associated with cell membranes. The reintroduction of wild-type LKB1 into a cancer cell line that lacks LKB1 suppressed growth, but mutants of LKB1 in which Ser(431) was mutated to Ala to prevent phosphorylation of LKB1 were ineffective in inhibiting growth. In contrast, a mutant of LKB1 that cannot be prenylated was still able to suppress the growth of cells.
机译：Peutz-Jeghers综合征是一种遗传性癌症综合征，导致受影响人群罹患肿瘤的风险大大增加。致病基因是一种蛋白激酶，称为LKB1，预计会起到抑癌作用。 LKB1在细胞中调控的机制尚不清楚。在这里，我们证明ERK1 / 2或cAMP依赖性蛋白激酶激活剂刺激Rat-2或胚胎干细胞可诱导Ser（431）内源性表达的LKB1磷酸化。我们目前提供的药理和遗传学证据表明p90（RSK）介导了激活ERK1 / 2激动剂的磷酸化，而cAMP依赖性蛋白激酶介导了激活活化腺苷酸环化酶的激动剂的磷酸化。 LKB1的Ser（431）与假定的异戊二烯基化基序相邻，并且我们证明了在293细胞中表达的全长LKB1通过在Cys（433）中添加法尼基基团而被异戊二烯基化。我们的数据表明，LKB1在Ser（431）的磷酸化不影响法呢基化，而法呢基化不影响Ser（431）的磷酸化。 LKB1在Ser（431）处的磷酸化不会改变LKB1自身或肿瘤抑制蛋白p53磷酸化的活性，也不会改变与细胞膜相关的LKB1的量。将野生型LKB1重新引入缺乏LKB1的癌细胞系可抑制生长，但是其中Ser（431）突变为Ala以防止LKB1磷酸化的LKB1突变体不能有效抑制生长。相反，不能被烯丙基化的LKB1突变体仍然能够抑制细胞的生长。

著录项

相似文献

  • 外文文献
  • 专利
代理获取

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号