Absence of both Sos-1 and Sos-2 in peripheral CD4(+) T cells leads to PI3K pathway activation and defects in migration

Eur J Immunol. 2015 Aug;45(8):2389-95. doi: 10.1002/eji.201445226. Epub 2015 Jun 5.

Abstract

Sos-1 and Sos-2 are ubiquitously expressed Ras-guanine exchange factors involved in Erk-MAP kinase pathway activation. Using mice lacking genes encoding Sos-1 and Sos-2, we evaluated the role of these proteins in peripheral T-cell signaling and function. Our results confirmed that TCR-mediated Erk activation in peripheral CD4(+) T cells does not depend on Sos-1 and Sos-2, although IL-2-mediated Erk activation does. Unexpectedly, however, we show an increase in AKT phosphorylation in Sos-1/2dKO CD4(+) T cells upon TCR and IL-2 stimulation. Activation of AKT was likely a consequence of increased recruitment of PI3K to Grb2 upon TCR and/or IL-2 stimulation in Sos-1/2dKO CD4(+) T cells. The increased activity of the PI3K/AKT pathway led to downregulation of the surface receptor CD62L in Sos-1/2dKO T cells and a subsequent impairment in T-cell migration.

Keywords: CD62L; Erk; Grb2; PI3K/AKT; Signaling; Sos; T cell.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Movement / genetics
  • Cell Movement / immunology*
  • Enzyme Activation / genetics
  • Enzyme Activation / immunology
  • GRB2 Adaptor Protein / genetics
  • GRB2 Adaptor Protein / immunology
  • Interleukin-2 / genetics
  • Interleukin-2 / immunology
  • L-Selectin / genetics
  • L-Selectin / immunology
  • Mice
  • Mice, Knockout
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / immunology*
  • Phosphorylation / genetics
  • Phosphorylation / immunology
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / immunology
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology
  • SOS1 Protein / genetics
  • SOS1 Protein / immunology*
  • Signal Transduction / genetics
  • Signal Transduction / immunology*
  • Son of Sevenless Proteins / genetics
  • Son of Sevenless Proteins / immunology*

Substances

  • GRB2 Adaptor Protein
  • Grb2 protein, mouse
  • Interleukin-2
  • Receptors, Antigen, T-Cell
  • SOS1 Protein
  • Son of Sevenless Proteins
  • Sos2 protein, mouse
  • L-Selectin
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt