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

ABSTRACT: 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.

SUBMITTER: Tripathi P

PROVIDER: S-EPMC3419974 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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

Tripathi Parul P Sahoo Naresh N Ullah Ubaid U Kallionpää Henna H Suneja Amita A Lahesmaa Riitta R Rao Kanury V S KV

Immunology and cell biology 20111011 7

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 init ...[more]

PMID: 21989417

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