Slow accumulation of active mitogen-activated protein kinase during thymocyte differentiation regulates the temporal pattern of transcription factor gene expression

Thymocyte-positive selection is believed to result from low affinity/avidit y interactions of TCR and MHC proteins, but how these weak interactions tra nslate into downstream biochemical signals and how such signals modulate ge ne expression is unknown. Using a culture system where isolated immature th ymocytes can be induced to differentiate along the CD4 lineage pathway, we show that sustained low level mitogen-activated protein/extracellular regul ated kinase activity is required for cell differentiation and survival. Fur thermore, induction of mitogen-activated protein/extracellular regulated ki nase activity is surprisingly slow under conditions that induce differentia tion. This pattern of kinase activity not only selects which genes are expr essed but also regulates the temporal pattern of expression of transcriptio n factor genes that are induced during double-positive thymocyte differenti ation.