Activation of the estrogen receptor through phosphorylation by mitogen-activated protein kinase.
Fiche publication
Date publication
décembre 1995
Journal
Science (New York, N.Y.)
Auteurs
Membres identifiés du Cancéropôle Est :
Pr CHAMBON Pierre, Dr METZGER Daniel
Tous les auteurs :
Kato S, Endoh H, Masuhiro Y, Kitamoto T, Uchiyama S, Sasaki H, Masushige S, Gotoh Y, Nishida E, Kawashima H, Metzger D, Chambon P
Lien Pubmed
Résumé
The phosphorylation of the human estrogen receptor (ER) serine residue at position 118 is required for full activity of the ER activation function 1 (AF-1). This Ser118 is phosphorylated by mitogen-activated protein kinase (MAPK) in vitro and in cells treated with epidermal growth factor (EGF) and insulin-like growth factor (IGF) in vivo. Overexpression of MAPK kinase (MAPKK) or of the guanine nucleotide binding protein Ras, both of which activate MAPK, enhanced estrogen-induced and antiestrogen (tamoxifen)-induced transcriptional activity of wild-type ER, but not that of a mutant ER with an alanine in place of Ser118. Thus, the activity of the amino-terminal AF-1 of the ER is modulated by the phosphorylation of Ser118 through the Ras-MAPK cascade of the growth factor signaling pathways.
Mots clés
Amino Acid Sequence, Animals, Calcium-Calmodulin-Dependent Protein Kinases, metabolism, Cell Line, Enzyme Activation, Epidermal Growth Factor, pharmacology, Estradiol, analogs & derivatives, Estrogen Antagonists, pharmacology, Humans, Mitogen-Activated Protein Kinase Kinases, Molecular Sequence Data, Mutation, Phosphorylation, Polyunsaturated Alkamides, Protein Kinases, metabolism, Protein-Serine-Threonine Kinases, metabolism, Proto-Oncogene Proteins, metabolism, Proto-Oncogene Proteins c-raf, Proto-Oncogene Proteins p21(ras), metabolism, Receptors, Estrogen, chemistry, Recombinant Fusion Proteins, metabolism, Serine, metabolism, Somatomedins, pharmacology, Tamoxifen, analogs & derivatives, Transcriptional Activation, drug effects, Transfection
Référence
Science. 1995 Dec;270(5241):1491-4