Paradoxical signaling pathways in developing thymocytes

  1. Get@NRC: Paradoxical signaling pathways in developing thymocytes (Opens in a new window)
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Journal titleJournal of Pharmacy and Pharmaceutical Sciences
Pages378386; # of pages: 9
Subjectadaptor protein; diacylglycerol; growth factor receptor bound protein 2; guanine nucleotide exchange factor; inositol trisphosphate; major histocompatibility antigen class 1; major histocompatibility antigen class 2; mitogen activated protein kinase; phosphatidylinositol 3 kinase; phosphatidylinositol 4,5 bisphosphate; phospholipase C gamma; protein kinase C; protein kinase Fyn; protein kinase Lck; protein kinase ZAP 70; protein p85; Ras protein; SOS protein; stress activated protein kinase; T lymphocyte receptor; transcription factor NFAT3; apoptosis; binding affinity; CD3+ T lymphocyte; CD4+ T lymphocyte; CD8+ T lymphocyte; cell differentiation; cell fate; cell maturation; cell selection; cell survival; complex formation; enzyme activation; enzyme activity; ligand binding; nonhuman; protein binding; protein phosphorylation; review; signal transduction; T lymphocyte; thymocyte; Animals; Antigens, CD3; Humans; Immune Tolerance; Intracellular Signaling Peptides and Proteins; Ligands; MAP Kinase Signaling System; Receptors, Antigen, T-Cell; Signal Transduction; Thymocytes
AbstractThymocytes are subjected to processes of selection during their life in the thymus; negative selection for autoreactive thymocytes and positive selection for self-MHC restricted self-tolerant cells. Interestingly, signals for positive or negative selection originate from the same receptor. More importantly, evidence showed that both death and survival signals are mediated by the MAPK pathway. The degree and order of ERK activation, but not other MAPK proteins, has been found to be different in either cases of cell fate. Therefore, it is suspected that the kinetics of ERK after activation may dictate cell death or survival. There are two important GEF proteins that are involved in Ras/ERK activation, RasGRP and SOS. It is thought that the level, order and kinetics of ERK are influenced upstream by the type of GEF. This review discusses the role of both GEF proteins in positive and negative selection and how this reflects on ERK activation.
Publication date
AffiliationNational Research Council Canada (NRC-CNRC); National Institute for Nanotechnology (NINT-INNT)
Peer reviewedYes
NPARC number21271563
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Record identifierfef50e42-e5e1-448c-96e6-f78d268cfb0f
Record created2014-03-24
Record modified2016-05-09
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