A ras signaling complex controls the RasC-TORC2 pathway and directed cell migration

Pascale G Charest, Zhouxin Shen, Ashley Lakoduk, Atsuo T. Sasaki, Steven P. Briggs, Richard A. Firtel

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

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 Sca1 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.

Original languageEnglish (US)
Pages (from-to)737-749
Number of pages13
JournalDevelopmental Cell
Volume18
Issue number5
DOIs
StatePublished - May 2010
Externally publishedYes

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Protein Phosphatase 2
Proto-Oncogene Proteins c-akt
Guanine
Cell Movement
Chemotaxis
Actins
Chemical activation
Dictyostelium
Chemotactic Factors
Cell membranes
Scaffolds
Cell Membrane
Membranes
Feedback
TOR complex 2

Keywords

  • Cellbio
  • Signaling

ASJC Scopus subject areas

  • Developmental Biology

Cite this

A ras signaling complex controls the RasC-TORC2 pathway and directed cell migration. / Charest, Pascale G; Shen, Zhouxin; Lakoduk, Ashley; Sasaki, Atsuo T.; Briggs, Steven P.; Firtel, Richard A.

In: Developmental Cell, Vol. 18, No. 5, 05.2010, p. 737-749.

Research output: Contribution to journalArticle

Charest, Pascale G ; Shen, Zhouxin ; Lakoduk, Ashley ; Sasaki, Atsuo T. ; Briggs, Steven P. ; Firtel, Richard A. / A ras signaling complex controls the RasC-TORC2 pathway and directed cell migration. In: Developmental Cell. 2010 ; Vol. 18, No. 5. pp. 737-749.
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