4.5 Article

Regulation of neuron survival through an intersectin-phosphoinositide 3'-kinase C2β-AKT pathway

期刊

MOLECULAR AND CELLULAR BIOLOGY
卷 27, 期 22, 页码 7906-7917

出版社

AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.01369-07

关键词

-

资金

  1. Medical Research Council [G0500936] Funding Source: researchfish
  2. MRC [G0500936] Funding Source: UKRI
  3. Intramural NIH HHS Funding Source: Medline
  4. Medical Research Council [G0500936] Funding Source: Medline

向作者/读者索取更多资源

While endocytosis attenuates signals from plasma membrane receptors, recent studies suggest that endocytosis also serves as a platform for the compartmentalized activation of cellular signaling pathways. Intersectin (ITSN) is a multidomain scaffolding protein that regulates endocytosis and has the potential to regulate various biochemical pathways through its multiple, modular domains. To address the biological importance of ITSN in regulating cellular signaling pathways versus in endocytosis, we have stably silenced ITSN expression in neuronal cells by using short hairpin RNAs. Decreasing ITSN expression dramatically increased apoptosis in both neuroblastoma cells and primary cortical neurons. Surprisingly, the loss of ITSN did not lead to major defects in the endocytic pathway. Yeast two-hybrid analysis identified class II phosphoinositide 3 '-kinase C2 beta PI3K-C2 beta as an ITSN binding protein, suggesting that ITSN may regulate a PI3K-C2 beta-AKT survival pathway. ITSN associated with PI3K-C2 beta on a subset of endomembrane vesicles and enhanced both basal and growth factor-stimulated PI3K-C2 beta activity, resulting in AKT activation. The use of pharmacological inhibitors, dominant negatives, and rescue experiments revealed that PI3K-C2 beta and AKT were epistatic to ITSN. This study represents the first demonstration that ITSN, independent of its role in endocytosis, regulates a critical cellular signaling pathway necessary for cell survival.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.5
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据