Cdc42 regulates GSK-3β and adenomatous polyposis coli to control cell polarity

被引:693
作者
Etienne-Manneville, S
Hall, A
机构
[1] UCL, MRC, Mol Cell Biol Lab, London WC1E 6BT, England
[2] UCL, Canc Res UK Oncogene & Signal Transduct Grp, Cell Biol Unit, London WC1E 6BT, England
[3] UCL, Dept Biochem & Mol Biol, London WC1E 6BT, England
基金
美国国家卫生研究院; 英国医学研究理事会;
关键词
D O I
10.1038/nature01423
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Cell polarity is a fundamental property of all cells. In higher eukaryotes, the small GTPase Cdc42, acting through a Par6-atypical protein kinase C (aPKC) complex, is required to establish cellular asymmetry during epithelial morphogenesis, asymmetric cell division and directed cell migration(1-5). However, little is known about what lies downstream of this complex. Here we show, through the use of primary rat astrocytes in a cell migration assay, that Par6-PKCzeta interacts directly with and regulates glycogen synthase kinase-3beta (GSK-3beta) to promote polarization of the centrosome and to control the direction of cell protrusion. Cdc42-dependent phosphorylation of GSK-3beta induces the interaction of adenomatous polyposis coli (Apc) protein with the plus ends of microtubules. The association of Apc with microtubules is essential for cell polarization. We conclude that Cdc42 regulates cell polarity through the spatial regulation of GSK-3beta and Apc. This role for Apc may contribute to its tumour-suppressor activity. occurs specifically at the leading edge of migrating cells, and
引用
收藏
页码:753 / 756
页数:5
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