Absence of Both Sos-1 and Sos-2 in Peripheral CD4(+) T cells Leads to PI3K Pathway Activation and Defects in Migration

Overview

Journal Eur J Immunol

Specialty Allergy & Immunology

Date 2015 May 15

PMID 25973715

Citations 17

Authors

Geoffrey Guittard

Robert L Kortum

Lakshmi Balagopalan

Nicolas Cuburu

Phan Nguyen

Connie L Sommers

Lawrence E Samelson

Affiliations

Soon will be listed here.

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.

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