The role of Erk1 and Erk2 in multiple stages of T cell development

Activation of extracellular-signal-regulated protein kinase (Erk) is central to growth-factor-receptor-mediated signaling including that originating from the T cell antigen receptor. It integrates cytoplasmic signals to effect changes in transcription associated with differentiation, proliferation, and survival. In this report, we present an analysis of mice with targeted deletions in Erk1 and Erk2 to assess the relationship between Erk activity and cell-cycle progression, thymocyte development, and lineage commitment. These studies show that Erk is selectively retained during beta selection-driven proliferation, and yet Erk1/2 are not required to complete differentiation to CD4(+)CD8(+) preselection stage of development. Erk activity is essential for the process of positive selection, and it differentially affects CD4 and CID8 T cell maturation; yet, diminished expression itself is not sufficient to alter lineage commitment.