| First Author | Marquis M | Year | 2014 |
| Journal | Mol Cell Biol | Volume | 34 |
| Issue | 18 | Pages | 3374-87 |
| PubMed ID | 25002529 | Mgi Jnum | J:224353 |
| Mgi Id | MGI:5662053 | Doi | 10.1128/MCB.01701-13 |
| Citation | Marquis M, et al. (2014) The catalytic activity of the mitogen-activated protein kinase extracellular signal-regulated kinase 3 is required to sustain CD4+ CD8+ thymocyte survival. Mol Cell Biol 34(18):3374-87 |
| abstractText | Extracellular signal-regulated kinase 3 (ERK3) is an atypical member of the mitogen-activated protein kinase (MAPK) family whose function is largely unknown. Given the central role of MAPKs in T cell development, we hypothesized that ERK3 may regulate thymocyte development. Here we have shown that ERK3 deficiency leads to a 50% reduction in CD4(+) CD8(+) (DP) thymocyte number. Analysis of hematopoietic chimeras revealed that the reduction in DP thymocytes is intrinsic to hematopoietic cells. We found that early thymic progenitors seed the Erk3(-/-) thymus and can properly differentiate and proliferate to generate DP thymocytes. However, ERK3 deficiency results in a decrease in the DP thymocyte half-life, associated with a higher level of apoptosis. As a consequence, ERK3-deficient DP thymocytes are impaired in their ability to make successful secondary T cell receptor alpha (TCRalpha) gene rearrangement. Introduction of an already rearranged TCR transgene restores thymic cell number. We further show that knock-in of a catalytically inactive allele of Erk3 fails to rescue the loss of DP thymocytes. Our results uncover a unique role for ERK3, dependent on its kinase activity, during T cell development and show that this atypical MAPK is essential to sustain DP survival during RAG-mediated rearrangements. |
