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

Geoffrey Guittard1, Robert L Kortum1, Lakshmi Balagopalan1

  • 1Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.

European Journal of Immunology
|May 15, 2015
PubMed

Insights

The study reveals that while Sos-1 and Sos-2 are not essential for T-cell receptor (TCR)-mediated Erk activation, they influence IL-2 signaling. Deletion of Sos-1 and Sos-2 in T cells unexpectedly enhances AKT signaling, impairing T-cell migration.

Area of Science:

  • Immunology
  • Cell Signaling
  • Molecular Biology

Background:

  • Son of Sevenless homolog 1 (Sos-1) and Son of Sevenless homolog 2 (Sos-2) are guanine nucleotide exchange factors crucial for Ras-MAPK pathway activation.
  • These proteins play a role in T-cell receptor (TCR) and cytokine signaling, impacting T-cell function.

Purpose of the Study:

  • To investigate the specific roles of Sos-1 and Sos-2 in peripheral T-cell signaling and function using knockout mouse models.
  • To elucidate the impact of Sos-1 and Sos-2 deficiency on Erk and AKT pathway activation in CD4(+) T cells.

Main Methods:

  • Generation and analysis of mice lacking genes for both Sos-1 and Sos-2 (Sos-1/2dKO).
  • Evaluation of T-cell signaling pathways, including Erk and AKT phosphorylation, following TCR and IL-2 stimulation.
  • Assessment of cell surface receptor expression (CD62L) and T-cell migration.

Main Results:

  • TCR-mediated Erk activation in peripheral CD4(+) T cells is independent of Sos-1 and Sos-2.
  • IL-2-mediated Erk activation, however, does depend on Sos-1 and Sos-2.
  • Sos-1/2dKO CD4(+) T cells exhibit increased AKT phosphorylation upon TCR and IL-2 stimulation, linked to enhanced PI3K recruitment to Grb2.
  • This heightened PI3K/AKT activity results in CD62L downregulation and impaired T-cell migration.

Conclusions:

  • Sos-1 and Sos-2 differentially regulate Erk and AKT pathways in peripheral T cells.
  • The absence of Sos-1 and Sos-2 leads to an aberrant PI3K/AKT activation, affecting T-cell function and migration.
  • These findings highlight a complex interplay between Sos proteins, TCR, IL-2, and downstream signaling cascades in T-cell biology.
Keywords:
CD62LErkGrb2PI3K/AKTSignalingSosT cell

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