title: Absence of both Sos-1 and Sos-2 in peripheral CD4(+) T cells leads to PI3K pathway activation and defects in migration.
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.
authors.affiliation: Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Guittard
authors.affiliation: Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Kortum
authors.affiliation: Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Balagopalan
authors.affiliation: Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Çuburu
authors.affiliation: Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Phan
authors.initials: P
authors.lastname: Nguyen
authors.affiliation: Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Connie L
authors.initials: CL
authors.lastname: Sommers
authors.affiliation: Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Lawrence E
authors.initials: LE
authors.lastname: Samelson
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D004789:Enzyme Activation / Q000235:genetics / Q000276:immunology; D051380:GRB2 Adaptor Protein / Q000235:genetics / Q000276:immunology; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology; D019041:L-Selectin / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000276:immunology*; D010766:Phosphorylation / Q000235:genetics / Q000276:immunology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D020837:SOS1 Protein / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D020664:Son of Sevenless Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D051380:GRB2 Adaptor Protein; C495949:Grb2 protein, mouse; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D020837:SOS1 Protein; D020664:Son of Sevenless Proteins; C116864:Sos2 protein, mouse; D019041:L-Selectin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: CD62L; Erk; Grb2; PI3K/AKT; Signaling; Sos; T cell