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We demonstrate that the mitogen‐activated protein kinases extracellular signal‐regulated kinase (ERK)‐1 and ERK‐2 have a central role in mediating T‐cell receptor‐dependent induction of  IL4  expression in human CD4 +  T cells. Significantly, this involved a novel mechanism wherein receptor cross‐linking induced activated ERK to physically associate with a promoter element on the  IL4  gene. The proximally localized ERK then facilitated recruitment of the key transcription factors necessary for initiating  IL4  gene transcription. Although both ERK‐1 and ERK‐2 bound to the promoter, recruitment of either one alone was found to be sufficient. We thus identify a novel mode of function for ERK wherein its physical association with the promoter serves as a prerequisite for enhanceosome assembly. This unusual pathway is also indispensable for human Th2‐cell differentiation.

A novel mechanism for ERK‐dependent regulation of IL4 transcription during human Th2‐cell differentiation