PMID- 23431403
OWN - NLM
STAT- MEDLINE
DCOM- 20130815
LR  - 20211203
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 2
DP  - 2013
TI  - Kinase suppressor of Ras 1 is not required for the generation of regulatory and 
      memory T cells.
PG  - e57137
LID - 10.1371/journal.pone.0057137 [doi]
LID - e57137
AB  - 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.
FAU - Le Borgne, Marie
AU  - Le Borgne M
AD  - Department of Pathology and Immunology, Washington University School of Medicine, 
      St Louis, Missouri, United States of America. mleborgne@wustl.edu
FAU - Filbert, Erin L
AU  - Filbert EL
FAU - Shaw, Andrey S
AU  - Shaw AS
LA  - eng
GR  - P30 DK020579/DK/NIDDK NIH HHS/United States
GR  - R37 AI057966/AI/NIAID NIH HHS/United States
GR  - HHMI/Howard Hughes Medical Institute/United States
GR  - NIH AI057966/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130219
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Multiprotein Complexes)
RN  - 0 (Proteins)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.- (KSR-1 protein kinase)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
SB  - IM
MH  - Animals
MH  - CD8-Positive T-Lymphocytes/*enzymology/immunology/physiology
MH  - Cell Differentiation
MH  - Cells, Cultured
MH  - Immunologic Memory
MH  - Listeria monocytogenes/immunology
MH  - Listeriosis/immunology
MH  - MAP Kinase Signaling System
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors
MH  - Multiprotein Complexes
MH  - Protein Kinases/*metabolism
MH  - Proteins/metabolism
MH  - T-Lymphocytes, Regulatory/*enzymology/immunology/physiology
MH  - TOR Serine-Threonine Kinases/metabolism
PMC - PMC3576348
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/02/23 06:00
MHDA- 2013/08/16 06:00
PMCR- 2013/02/19
CRDT- 2013/02/23 06:00
PHST- 2012/09/11 00:00 [received]
PHST- 2013/01/21 00:00 [accepted]
PHST- 2013/02/23 06:00 [entrez]
PHST- 2013/02/23 06:00 [pubmed]
PHST- 2013/08/16 06:00 [medline]
PHST- 2013/02/19 00:00 [pmc-release]
AID - PONE-D-12-27710 [pii]
AID - 10.1371/journal.pone.0057137 [doi]
PST - ppublish
SO  - PLoS One. 2013;8(2):e57137. doi: 10.1371/journal.pone.0057137. Epub 2013 Feb 19.