Publication Date:
1995-12-01
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kato, S -- Endoh, H -- Masuhiro, Y -- Kitamoto, T -- Uchiyama, S -- Sasaki, H -- Masushige, S -- Gotoh, Y -- Nishida, E -- Kawashima, H -- Metzger, D -- Chambon, P -- New York, N.Y. -- Science. 1995 Dec 1;270(5241):1491-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Agricultural Chemistry, Tokyo University of Agriculture, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7491495" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Sequence
;
Animals
;
Calcium-Calmodulin-Dependent Protein Kinases/*metabolism
;
Cell Line
;
Enzyme Activation
;
Epidermal Growth Factor/pharmacology
;
Estradiol/analogs & derivatives/pharmacology
;
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/genetics/*metabolism
;
Recombinant Fusion Proteins/metabolism
;
Serine/*metabolism
;
Somatomedins/pharmacology
;
Tamoxifen/analogs & derivatives/pharmacology
;
*Transcriptional Activation/drug effects
;
Transfection
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
