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

Dev Cell. 2010 May 18;18(5):737-49. doi: 10.1016/j.devcel.2010.03.017.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Aggregation / physiology
  • Cell Membrane / physiology
  • Cell Movement / physiology*
  • Chemotaxis / physiology*
  • Cyclic AMP / physiology
  • Dictyostelium / physiology
  • Gene Deletion
  • Humans
  • Neutrophils / cytology
  • Neutrophils / physiology*
  • Phosphorylation
  • Proto-Oncogene Proteins p21(ras) / physiology
  • Protozoan Proteins / physiology
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • ras Guanine Nucleotide Exchange Factors / physiology
  • ras Proteins / genetics
  • ras Proteins / physiology*


  • CRTC2 protein, human
  • Protozoan Proteins
  • Transcription Factors
  • aimless protein, Dictyostelium
  • ras Guanine Nucleotide Exchange Factors
  • Cyclic AMP
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins