The catalytic activity of the mitogen-activated protein kinase extracellular signal-regulated kinase 3 is required to sustain CD4+ CD8+ thymocyte survival.

摘要: Extracellular signal-regulated kinase 3 (ERK3) is an atypical member of the mitogen-activated protein (MAPK) family whose function largely unknown. Given central role MAPKs in T cell development, we hypothesized that ERK3 may regulate thymocyte development. Here have shown deficiency leads to a 50% reduction CD4+ CD8+ (DP) number. Analysis hematopoietic chimeras revealed DP thymocytes intrinsic cells. We found early thymic progenitors seed Erk3−/− thymus and can properly differentiate proliferate generate thymocytes. However, results decrease half-life, associated with higher level apoptosis. As consequence, ERK3-deficient are impaired their ability make successful secondary receptor alpha (TCRα) gene rearrangement. Introduction already rearranged TCR transgene restores further show knock-in catalytically inactive allele Erk3 fails rescue loss Our uncover unique for ERK3, dependent on its activity, during development this MAPK essential sustain survival RAG-mediated rearrangements.