PI 3激酶和PTEN对3-磷酸肌醇的时空调节介导趋化作用。

Spatial and temporal regulation of 3-phosphoinositides by PI 3-kinase and PTEN mediates chemotaxis.

作者信息

Funamoto Satoru, Meili Ruedi, Lee Susan, Parry Lisa, Firtel Richard A

机构信息

Section of Cell and Developmental Biology, Division of Biology, Center for Molecular Genetics, University of California, San Diego, La Jolla, CA 92093, USA.

出版信息

Cell. 2002 May 31;109(5):611-23. doi: 10.1016/s0092-8674(02)00755-9.

DOI:10.1016/s0092-8674(02)00755-9

PMID:12062104

Abstract

We have investigated the mechanisms of leading edge formation in chemotaxing Dictyostelium cells. We demonstrate that while phosphatidylinositol 3-kinase (PI3K) transiently translocates to the plasma membrane in response to chemoattractant stimulation and to the leading edge in chemotaxing cells, PTEN, a negative regulator of PI3K pathways, exhibits a reciprocal pattern of localization. By uniformly localizing PI3K along the plasma membrane, we show that chemotaxis pathways are activated along the lateral sides of cells and PI3K can initiate pseudopod formation, providing evidence for a direct instructional role of PI3K in leading edge formation. These findings provide evidence that differential subcellular localization and activation of PI3K and PTEN is required for proper chemotaxis.

摘要

我们研究了趋化性盘基网柄菌细胞前缘形成的机制。我们证明，虽然磷脂酰肌醇3激酶（PI3K）在趋化因子刺激下会短暂地转运到质膜，并在趋化细胞的前缘出现，但PI3K信号通路的负调节因子PTEN则呈现出相反的定位模式。通过使PI3K在质膜上均匀定位，我们发现趋化信号通路在细胞侧面被激活，且PI3K可启动伪足形成，这为PI3K在细胞前缘形成中起直接指导作用提供了证据。这些发现证明，PI3K和PTEN在亚细胞水平上的差异定位和激活是正常趋化作用所必需的。