title: 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.
authors: Immunology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
authors: Parul
authors: P
authors: Tripathi
authors: Naresh
authors: N
authors: Sahoo
authors: Ubaid
authors: U
authors: Ullah
authors: Henna
authors: H
authors: Kallionpää
authors: Amita
authors: A
authors: Suneja
authors: Riitta
authors: R
authors: Lahesmaa
authors: Kanury V S
authors: KV
authors: Rao
mesh_terms: D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D002454:Cell Differentiation; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D005786:Gene Expression Regulation; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics*; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D034622:RNA Interference; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018418:Th2 Cells / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D007376:Interleukin-2; D015847:Interleukin-4; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3