Activation of the estrogen receptor through phosphorylation by mitogen-activated protein kinase.
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.
D000595:Amino Acid Sequence; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002460:Cell Line; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D006801:Humans; D020929:Mitogen-Activated Protein Kinase Kinases; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D053284:Polyunsaturated Alkamides; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D011960:Receptors, Estrogen / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012694:Serine / Q000378:metabolism*; D013002:Somatomedins / Q000494:pharmacology; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection
D004965:Estrogen Antagonists; D053284:Polyunsaturated Alkamides; D011518:Proto-Oncogene Proteins; D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins; D013002:Somatomedins; D013629:Tamoxifen; C016601:afimoxifene; D012694:Serine; D004958:Estradiol; D004815:Epidermal Growth Factor; C051781:ICI 164384; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)