Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 45, Issue 8, Pages 2389-2395Publisher
WILEY-BLACKWELL
DOI: 10.1002/eji.201445226
Keywords
CD62L; Erk; Grb2; PI3K/AKT; Sos; Signaling; T cell
Categories
Funding
- Center for Cancer Research, NCI, NIH
- NATIONAL CANCER INSTITUTE [ZIABC010304] Funding Source: NIH RePORTER
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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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