title: Kinase suppressor of Ras 1 is not required for the generation of regulatory and memory T cells.
abstract: The mammalian target of rapamycin (mTOR) kinase is a critical regulator of the differentiation of helper and regulatory CD4+ T cells, as well as memory CD8+ T cells. In this study, we investigated the role of the ERK signaling pathway in regulating mTOR activation in T cells. We showed that activation of ERK following TCR engagement is required for sustained mTOR complex 1 (mTORC1) activation. Absence of kinase suppressor of Ras 1 (KSR1), a scaffold protein of the ERK signaling pathway, or inhibition of ERK resulted in decreased mTORC1 activity following T cell activation. However, KSR1-deficient mice displayed normal regulatory CD4+ T cell development, as well as normal memory CD8+ T cell responses to LCMV and Listeria monocytogenes infection. These data indicate that despite its role in mTORC1 activation, KSR1 is not required in vivo for mTOR-dependent T cell differentiation.
authors: Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri, United States of America. mleborgne@wustl.edu
authors: Marie
authors: M
authors: Le Borgne
authors: Erin L
authors: EL
authors: Filbert
authors: Andrey S
authors: AS
authors: Shaw
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000201:enzymology* / Q000276:immunology / Q000502:physiology; D002454:Cell Differentiation; D002478:Cells, Cultured; D007156:Immunologic Memory; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000276:immunology; D020935:MAP Kinase Signaling System; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D046912:Multiprotein Complexes; D011494:Protein Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000201:enzymology* / Q000276:immunology / Q000502:physiology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D046912:Multiprotein Complexes; D011506:Proteins; D011494:Protein Kinases; C097199:KSR-1 protein kinase; C546843:mTOR protein, mouse; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D020929:Mitogen-Activated Protein Kinase Kinases