Guittard Geoffrey, Kortum Robert L, Balagopalan Lakshmi, Çuburu Nicolas, Nguyen Phan, Sommers Connie L, Samelson Lawrence E
Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Eur J Immunol. 2015 Aug;45(8):2389-95. doi: 10.1002/eji.201445226. Epub 2015 Jun 5.
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.
Eur J Immunol. 2014-2-20
Proc Natl Acad Sci U S A. 2011-7-11
Methods Mol Biol. 2021
Front Physiol. 2021-4-6
Int J Med Sci. 2020-2-17
Eur J Immunol. 2014-2-20
Trends Immunol. 2013-3-15
Mol Cell Biol. 2012-5-14
Proc Natl Acad Sci U S A. 2011-7-11
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