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A novel mechanism for ERK‐dependent regulation of IL4 transcription during human Th2‐cell differentiation
Author(s) -
Tripathi Parul,
Sahoo Naresh,
Ullah Ubaid,
Kallionpää Henna,
Suneja Amita,
Lahesmaa Riitta,
Rao Kanury V S
Publication year - 2012
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2011.87
Subject(s) - mapk/erk pathway , microbiology and biotechnology , transcription factor , kinase , biology , transcription (linguistics) , protein kinase a , signal transduction , gene , genetics , linguistics , philosophy
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.