...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >Cellular Activation Triggered by the Autosomal Dominant Polycystic Kidney Disease Gene Product PKD2
【24h】

Cellular Activation Triggered by the Autosomal Dominant Polycystic Kidney Disease Gene Product PKD2

机译：常染色体显性多囊肾疾病基因产物PKD2触发的细胞活化。

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Autosomal dominant polycystic kidney disease (ADPKD) is caused by germ line mutations in at least three ADPKD genes. Two recently isolated ADPKD genes, PKD1 and PKD2, encode integral membrane proteins of unknown function. We found that PKD2 upregulated AP-1-dependent transcription in human embryonic kidney 293T cells. The PKD2-mediated AP-1 activity was dependent upon activation of the mitogen-activated protein kinases p38 and JNK1 and protein kinase C (PKC) ?, a calcium-independent PKC isozyme. Staurosporine, but not the calcium chelator BAPTA [1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetate], inhibited PKD2-mediated signaling, consistent with the involvement of a calcium-independent PKC isozyme. Coexpression of PKD2 with the interacting C terminus of PKD1 dramatically augmented PKD2-mediated AP-1 activation. The synergistic signaling between PKD1 and PKD2 involved the activation of two distinct PKC isozymes, PKC α and PKC ?, respectively. Our findings are consistent with others that support a functional connection between PKD1 and PKD2 involving multiple signaling pathways that converge to induce AP-1 activity, a transcription factor that regulates different cellular programs such as proliferation, differentiation, and apoptosis. Activation of these signaling cascades may promote the full maturation of developing tubular epithelial cells, while inactivation of these signaling cascades may impair terminal differentiation and facilitate the development of renal tubular cysts.
机译：常染色体显性遗传性多囊肾疾病（ADPKD）是由至少三个ADPKD基因中的种系突变引起的。最近分离的两个ADPKD基因 PKD1 和 PKD2 编码未知功能的整合膜蛋白。我们发现PKD2上调人类胚胎肾脏293T细胞中的AP-1依赖性转录。 PKD2介导的AP-1活性取决于有丝分裂原活化的蛋白激酶p38和JNK1和蛋白激酶C（PKC）β（一种不依赖钙的PKC同工酶）的激活。星形孢菌素，而不是钙螯合剂BAPTA [1,2-双（ o -氨基苯氧基）乙烷- N ， N ， N '， N '-四乙酸盐]抑制PKD2介导的信号传导，与不依赖钙的PKC同工酶的参与一致。 PKD2与PKD1的相互作用C末端的共表达大大增强了PKD2介导的AP-1激活。 PKD1和PKD2之间的协同信号传导涉及两种不同的PKC同工酶PKCα和PKCα的激活。我们的发现与其他人支持PKD1和PKD2之间的功能连接的研究结果一致，这些功能连接涉及多个信号通路，这些信号通路会聚合以诱导AP-1活性，AP-1活性是调节不同细胞程序（例如增殖，分化和凋亡）的转录因子。这些信号级联的激活可以促进发育中的肾小管上皮细胞的完全成熟，而这些信号级联的失活可以损害终末分化并促进肾小管囊肿的发展。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

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