A Ras Signaling Complex Controls the RasC-TORC2 Pathway and Directed Cell Migration

被引：116

作者：

Charest, Pascale G. ^{[1
]}

Shen, Zhouxin ^{[1
]}

Lakoduk, Ashley ^{[1
]}

Sasaki, Atsuo T. ^{[1
]}

Briggs, Steven P. ^{[1
]}

Firtel, Richard A. ^{[1
]}

机构：

[1] Univ Calif San Diego, Div Biol Sci, Sect Cell & Dev Biol, La Jolla, CA 92093 USA

来源：

DEVELOPMENTAL CELL | 2010年 / 18卷 / 05期

基金：

美国国家卫生研究院;

关键词：

ADENYLYL-CYCLASE; LEADING-EDGE; DICTYOSTELIUM; ACTIVATION; CHEMOTAXIS; KINASE; CAMP; PROTEINS; 3-KINASE; AKT/PKB;

D O I：

10.1016/j.devcel.2010.03.017

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Ras was found to regulate Dictyostelium chemotaxis, but the mechanisms that spatially and temporally control Ras activity during chemotaxis remain largely unknown. We report the discovery of a Ras signaling complex that includes the Ras guanine exchange factor (RasGEF) Aimless, RasGEFH, protein phosphatase 2A (PP2A), and a scaffold designated Sca1. The Sca1/RasGEF/PP2A complex is recruited to the plasma membrane in a chemoattractant- and F-actin-dependent manner and is enriched at the leading edge of chemotaxing cells where it regulates F-actin dynamics and signal relay by controlling the activation of RasC and the downstream target of rapamycin complex 2 (TORC2)-Akt/protein kinase B (PKB) pathway. In addition, PKB and PKB-related PKBR1 phosphorylate Scal and regulate the membrane localization of the Sca1/RasGEF/PP2A complex, and thereby RasC activity, in a negative feedback fashion. Thus, our study uncovered a molecular mechanism whereby RasC activity and the spatiotemporal activation of TORC2 are tightly controlled at the leading edge of chemotaxing cells.

引用

页码：737 / 749

页数：13

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