Activation of the unliganded estrogen receptor by EGF involves the MAP kinase pathway and direct phosphorylation.

作者: G. Bunone , P. A. Briand , R. J. Miksicek , D. Picard

DOI: 10.1002/J.1460-2075.1996.TB00571.X

关键词: MAPK/ERK pathwaySignal transductionEstrogen receptorBiologyCancer researchEpidermal growth factorMAP kinase kinase kinasePhosphorylationMitogen-activated protein kinaseKinase

摘要: Abstract The estrogen receptor (ER) can be activated as a transcription factor either by binding of cognate estrogenic ligand or, indirectly, variety other extracellular signals. As first step towards elucidating the mechanism 'steroid-independent activation' ER epidermal growth (EGF), we have mapped target domain and determined signaling pathway. We show that N-terminal transcriptional activation function AF-1, but not C-terminal AF-2, is necessary for EGF response. Both EGF-induced hyperphosphorylation unliganded depend on phosphorylatable serine residue at position 118. However, its phosphorylation sufficient and, hence, there must domains or proteins which fulfill an additional requirement through ER. Using dominant-negative Ras MAP kinase (MAPK kinase) constitutively active MAPK mutants, activates pathway suggesting directly phosphorylates critical Our results also imply steroid-independent arise during malignant progression breast tumors, may contribute to tamoxifen resistance.

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