Crossref journal-article
American Association for the Advancement of Science (AAAS)
Science (221)
Abstract

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 Ser 118 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 Ser 118 . Thus, the activity of the amino-terminal AF-1 of the ER is modulated by the phosphorylation of Ser 118 through the Ras-MAPK cascade of the growth factor signaling pathways.

Bibliography

Kato, S., Endoh, H., Masuhiro, Y., Kitamoto, T., Uchiyama, S., Sasaki, H., Masushige, S., Gotoh, Y., Nishida, E., Kawashima, H., Metzger, D., & Chambon, P. (1995). Activation of the Estrogen Receptor Through Phosphorylation by Mitogen-Activated Protein Kinase. Science, 270(5241), 1491–1494.

Authors 12
  1. Shigeaki Kato (first)
  2. Hideki Endoh (additional)
  3. Yoshikazu Masuhiro (additional)
  4. Takuya Kitamoto (additional)
  5. Shimami Uchiyama (additional)
  6. Haruna Sasaki (additional)
  7. Shoichi Masushige (additional)
  8. Yukiko Gotoh (additional)
  9. Eisuke Nishida (additional)
  10. Hiroyuki Kawashima (additional)
  11. Daniel Metzger (additional)
  12. Pierre Chambon (additional)
References 47 Referenced 1,507
  1. ALI S, MODULATION OF TRANSCRIPTIONAL ACTIVATION BY LIGAND-DEPENDENT PHOSPHORYLATION OF THE HUMAN ESTROGEN RECEPTOR-A/B REGION, EMBO JOURNAL 12, 1153 (1993). (10.1002/j.1460-2075.1993.tb05756.x) / EMBO JOURNAL / MODULATION OF TRANSCRIPTIONAL ACTIVATION BY LIGAND-DEPENDENT PHOSPHORYLATION OF THE HUMAN ESTROGEN RECEPTOR-A/B REGION by ALI S (1993)
  2. ARNOLD S.F., IN-VIVO AND IN-VITRO PHOSPHORYLATION OF THE HUMAN ESTROGEN-RECEPTOR, JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY 52, 159 (1995). (10.1016/0960-0760(94)00166-J) / JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY / IN-VIVO AND IN-VITRO PHOSPHORYLATION OF THE HUMAN ESTROGEN-RECEPTOR by ARNOLD S.F. (1995)
  3. ARONICA S.M., STIMULATION OF ESTROGEN RECEPTOR-MEDIATED TRANSCRIPTION AND ALTERATION IN THE PHOSPHORYLATION STATE OF THE RAT UTERINE ESTROGEN-RECEPTOR BY ESTROGEN, CYCLIC ADENOSINE-MONOPHOSPHATE, AND INSULIN-LIKE GROWTH FACTOR-I, MOLECULAR ENDOCRINOLOGY 7, 743 (1993). / MOLECULAR ENDOCRINOLOGY / STIMULATION OF ESTROGEN RECEPTOR-MEDIATED TRANSCRIPTION AND ALTERATION IN THE PHOSPHORYLATION STATE OF THE RAT UTERINE ESTROGEN-RECEPTOR BY ESTROGEN, CYCLIC ADENOSINE-MONOPHOSPHATE, AND INSULIN-LIKE GROWTH FACTOR-I by ARONICA S.M. (1993)
  4. BEATO M, GENE-REGULATION BY STEROID-HORMONES, CELL 56, 335 (1989). (10.1016/0092-8674(89)90237-7) / CELL / GENE-REGULATION BY STEROID-HORMONES by BEATO M (1989)
  5. BERRY M, ROLE OF THE 2 ACTIVATING DOMAINS OF THE ESTROGEN-RECEPTOR IN THE CELL-TYPE AND PROMOTER-CONTEXT DEPENDENT AGONISTIC ACTIVITY OF THE ANTIESTROGEN 4-HYDROXYTAMOXIFEN, EMBO JOURNAL 9, 2811 (1990). (10.1002/j.1460-2075.1990.tb07469.x) / EMBO JOURNAL / ROLE OF THE 2 ACTIVATING DOMAINS OF THE ESTROGEN-RECEPTOR IN THE CELL-TYPE AND PROMOTER-CONTEXT DEPENDENT AGONISTIC ACTIVITY OF THE ANTIESTROGEN 4-HYDROXYTAMOXIFEN by BERRY M (1990)
  6. BRUNNER N, MCF7/LCC2 - A 4-HYDROXYTAMOXIFEN RESISTANT HUMAN BREAST-CANCER VARIANT THAT RETAINS SENSITIVITY TO THE STEROIDAL ANTIESTROGEN ICI-182,780, CANCER RESEARCH 53, 3229 (1993). / CANCER RESEARCH / MCF7/LCC2 - A 4-HYDROXYTAMOXIFEN RESISTANT HUMAN BREAST-CANCER VARIANT THAT RETAINS SENSITIVITY TO THE STEROIDAL ANTIESTROGEN ICI-182,780 by BRUNNER N (1993)
  7. DANIELIAN P.S., IDENTIFICATION OF A CONSERVED REGION REQUIRED FOR HORMONE DEPENDENT TRANSCRIPTIONAL ACTIVATION BY STEROID-HORMONE RECEPTORS, EMBO JOURNAL 11, 1025 (1992). (10.1002/j.1460-2075.1992.tb05141.x) / EMBO JOURNAL / IDENTIFICATION OF A CONSERVED REGION REQUIRED FOR HORMONE DEPENDENT TRANSCRIPTIONAL ACTIVATION BY STEROID-HORMONE RECEPTORS by DANIELIAN P.S. (1992)
  8. DENTON R.R., ESTROGEN-RECEPTOR PHOSPHORYLATION - HORMONAL DEPENDENCE AND CONSEQUENCE ON SPECIFIC DNA-BINDING, JOURNAL OF BIOLOGICAL CHEMISTRY 267, 7263 (1992). (10.1016/S0021-9258(18)42514-8) / JOURNAL OF BIOLOGICAL CHEMISTRY / ESTROGEN-RECEPTOR PHOSPHORYLATION - HORMONAL DEPENDENCE AND CONSEQUENCE ON SPECIFIC DNA-BINDING by DENTON R.R. (1992)
  9. EFREMIDIS A.P., CANCER J 2, 288 (1989). / CANCER J by EFREMIDIS A.P. (1989)
  10. 10.1126/science.3283939
  11. FUJIOKA H, TRANSFORMING AND C-FOS PROMOTER ENHANCER-STIMULATING ACTIVITIES OF A STIMULATORY GDP GTP EXCHANGE PROTEIN FOR SMALL GTP-BINDING PROTEINS, JOURNAL OF BIOLOGICAL CHEMISTRY 267, 926 (1992). (10.1016/S0021-9258(18)48373-1) / JOURNAL OF BIOLOGICAL CHEMISTRY / TRANSFORMING AND C-FOS PROMOTER ENHANCER-STIMULATING ACTIVITIES OF A STIMULATORY GDP GTP EXCHANGE PROTEIN FOR SMALL GTP-BINDING PROTEINS by FUJIOKA H (1992)
  12. GONZALEZ F.A., IDENTIFICATION OF SUBSTRATE RECOGNITION DETERMINANTS FOR HUMAN ERK1 AND ERK2 PROTEIN-KINASES, JOURNAL OF BIOLOGICAL CHEMISTRY 266, 22159 (1991). (10.1016/S0021-9258(18)54548-8) / JOURNAL OF BIOLOGICAL CHEMISTRY / IDENTIFICATION OF SUBSTRATE RECOGNITION DETERMINANTS FOR HUMAN ERK1 AND ERK2 PROTEIN-KINASES by GONZALEZ F.A. (1991)
  13. GOTOH Y, INVOLVEMENT OF THE MAP KINASE CASCADE IN XENOPUS MESODERM INDUCTION, EMBO JOURNAL 14, 2491 (1995). (10.1002/j.1460-2075.1995.tb07246.x) / EMBO JOURNAL / INVOLVEMENT OF THE MAP KINASE CASCADE IN XENOPUS MESODERM INDUCTION by GOTOH Y (1995)
  14. GOTOH Y, INVITRO EFFECTS ON MICROTUBULE DYNAMICS OF PURIFIED XENOPUS M-PHASE-ACTIVATED MAP KINASE, NATURE 349, 251 (1991). (10.1038/349251a0) / NATURE / INVITRO EFFECTS ON MICROTUBULE DYNAMICS OF PURIFIED XENOPUS M-PHASE-ACTIVATED MAP KINASE by GOTOH Y (1991)
  15. GOTOH Y, CHARACTERIZATION OF RECOMBINANT XENOPUS MAP KINASE KINASES MUTATED AT POTENTIAL PHOSPHORYLATION SITES, ONCOGENE 9, 1891 (1994). / ONCOGENE / CHARACTERIZATION OF RECOMBINANT XENOPUS MAP KINASE KINASES MUTATED AT POTENTIAL PHOSPHORYLATION SITES by GOTOH Y (1994)
  16. GOTTARDIS M.M., DEVELOPMENT OF TAMOXIFEN-STIMULATED GROWTH OF MCF-7 TUMORS IN ATHYMIC MICE AFTER LONG-TERM ANTIESTROGEN ADMINISTRATION, CANCER RESEARCH 48, 5183 (1988). / CANCER RESEARCH / DEVELOPMENT OF TAMOXIFEN-STIMULATED GROWTH OF MCF-7 TUMORS IN ATHYMIC MICE AFTER LONG-TERM ANTIESTROGEN ADMINISTRATION by GOTTARDIS M.M. (1988)
  17. GREEN S, NUCLEAR RECEPTORS ENHANCE OUR UNDERSTANDING OF TRANSCRIPTION REGULATION, TRENDS IN GENETICS 4, 309 (1988). (10.1016/0168-9525(88)90108-4) / TRENDS IN GENETICS / NUCLEAR RECEPTORS ENHANCE OUR UNDERSTANDING OF TRANSCRIPTION REGULATION by GREEN S (1988)
  18. GRONEMEYER H, TRANSCRIPTION ACTIVATION BY ESTROGEN AND PROGESTERONE RECEPTORS, ANNUAL REVIEW OF GENETICS 25, 89 (1991). (10.1146/annurev.ge.25.120191.000513) / ANNUAL REVIEW OF GENETICS / TRANSCRIPTION ACTIVATION BY ESTROGEN AND PROGESTERONE RECEPTORS by GRONEMEYER H (1991)
  19. GULLICK W.J., PROG GROWTH FACTOR R 2, 1 (1990). (10.1016/0955-2235(90)90006-6) / PROG GROWTH FACTOR R by GULLICK W.J. (1990)
  20. HARRIS A.L., BREAST CANCER CELLUL 93, (1988). / BREAST CANCER CELLUL by HARRIS A.L. (1988)
  21. HILL C.S., TRANSCRIPTIONAL REGULATION BY EXTRACELLULAR SIGNALS - MECHANISMS AND SPECIFICITY, CELL 80, 199 (1995). (10.1016/0092-8674(95)90403-4) / CELL / TRANSCRIPTIONAL REGULATION BY EXTRACELLULAR SIGNALS - MECHANISMS AND SPECIFICITY by HILL C.S. (1995)
  22. IGNARTROWBRIDGE D.M., PEPTIDE GROWTH-FACTORS ELICIT ESTROGEN RECEPTOR-DEPENDENT TRANSCRIPTIONAL ACTIVATION OF AN ESTROGEN-RESPONSIVE ELEMENT, MOLECULAR ENDOCRINOLOGY 7, 992 (1993). / MOLECULAR ENDOCRINOLOGY / PEPTIDE GROWTH-FACTORS ELICIT ESTROGEN RECEPTOR-DEPENDENT TRANSCRIPTIONAL ACTIVATION OF AN ESTROGEN-RESPONSIVE ELEMENT by IGNARTROWBRIDGE D.M. (1993)
  23. JANES P.W., ACTIVATION OF THE RAS SIGNALING PATHWAY IN HUMAN BREAST-CANCER CELLS OVEREXPRESSING ERBB-2, ONCOGENE 9, 3601 (1994). / ONCOGENE / ACTIVATION OF THE RAS SIGNALING PATHWAY IN HUMAN BREAST-CANCER CELLS OVEREXPRESSING ERBB-2 by JANES P.W. (1994)
  24. JOEL P.B., ESTRADIOL AND PHORBOL ESTER CAUSE PHOSPHORYLATION OF SERINE-118 IN THE HUMAN ESTROGEN-RECEPTOR, MOLECULAR ENDOCRINOLOGY 9, 1041 (1995). / MOLECULAR ENDOCRINOLOGY / ESTRADIOL AND PHORBOL ESTER CAUSE PHOSPHORYLATION OF SERINE-118 IN THE HUMAN ESTROGEN-RECEPTOR by JOEL P.B. (1995)
  25. JORDAN V.C., EFFECTS OF ANTIESTROGENS ON BONE IN CASTRATED AND INTACT FEMALE RATS, BREAST CANCER RESEARCH AND TREATMENT 10, 31 (1987). (10.1007/BF01806132) / BREAST CANCER RESEARCH AND TREATMENT / EFFECTS OF ANTIESTROGENS ON BONE IN CASTRATED AND INTACT FEMALE RATS by JORDAN V.C. (1987)
  26. KASTNER P, VITAMIN A HLTH DIS 189, (1994). / VITAMIN A HLTH DIS by KASTNER P (1994)
  27. KATO S, A FAR UPSTREAM ESTROGEN RESPONSE ELEMENT OF THE OVALBUMIN GENE CONTAINS SEVERAL HALF-PALINDROMIC 5′-TGACC-3′ MOTIFS ACTING SYNERGISTICALLY, CELL 68, 731 (1992). (10.1016/0092-8674(92)90148-6) / CELL / A FAR UPSTREAM ESTROGEN RESPONSE ELEMENT OF THE OVALBUMIN GENE CONTAINS SEVERAL HALF-PALINDROMIC 5′-TGACC-3′ MOTIFS ACTING SYNERGISTICALLY by KATO S (1992)
  28. KATO S unpublished data.
  29. KUMAR V, FUNCTIONAL DOMAINS OF THE HUMAN ESTROGEN-RECEPTOR, CELL 51, 941 (1987). (10.1016/0092-8674(87)90581-2) / CELL / FUNCTIONAL DOMAINS OF THE HUMAN ESTROGEN-RECEPTOR by KUMAR V (1987)
  30. LEES J.A., IDENTIFICATION OF CONSTITUTIVE AND STEROID-DEPENDENT TRANSACTIVATION DOMAINS IN THE MOUSE ESTROGEN-RECEPTOR, JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY 34, 33 (1989). (10.1016/0022-4731(89)90063-0) / JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY / IDENTIFICATION OF CONSTITUTIVE AND STEROID-DEPENDENT TRANSACTIVATION DOMAINS IN THE MOUSE ESTROGEN-RECEPTOR by LEES J.A. (1989)
  31. LEGOFF P, PHOSPHORYLATION OF THE HUMAN ESTROGEN-RECEPTOR - IDENTIFICATION OF HORMONE-REGULATED SITES AND EXAMINATION OF THEIR INFLUENCE ON TRANSCRIPTIONAL ACTIVITY, JOURNAL OF BIOLOGICAL CHEMISTRY 269, 4458 (1994). (10.1016/S0021-9258(17)41801-1) / JOURNAL OF BIOLOGICAL CHEMISTRY / PHOSPHORYLATION OF THE HUMAN ESTROGEN-RECEPTOR - IDENTIFICATION OF HORMONE-REGULATED SITES AND EXAMINATION OF THEIR INFLUENCE ON TRANSCRIPTIONAL ACTIVITY by LEGOFF P (1994)
  32. LOVE R.R., BONE-MINERAL DENSITY IN WOMEN WITH BREAST-CANCER TREATED WITH ADJUVANT TAMOXIFEN FOR AT LEAST 2 YEARS, BREAST CANCER RESEARCH AND TREATMENT 12, 297 (1988). (10.1007/BF01811242) / BREAST CANCER RESEARCH AND TREATMENT / BONE-MINERAL DENSITY IN WOMEN WITH BREAST-CANCER TREATED WITH ADJUVANT TAMOXIFEN FOR AT LEAST 2 YEARS by LOVE R.R. (1988)
  33. MANGELSDORF D.J., RETINOIDS: CH8 (1994). / RETINOIDS by MANGELSDORF D.J. (1994)
  34. MARSHALL C.J., SPECIFICITY OF RECEPTOR TYROSINE KINASE SIGNALING - TRANSIENT VERSUS SUSTAINED EXTRACELLULAR SIGNAL-REGULATED KINASE ACTIVATION, CELL 80, 179 (1995). (10.1016/0092-8674(95)90401-8) / CELL / SPECIFICITY OF RECEPTOR TYROSINE KINASE SIGNALING - TRANSIENT VERSUS SUSTAINED EXTRACELLULAR SIGNAL-REGULATED KINASE ACTIVATION by MARSHALL C.J. (1995)
  35. MASON S, TYPE-1 GROWTH-FACTOR RECEPTORS - AN OVERVIEW OF RECENT DEVELOPMENTS, BREAST 4, 11 (1995). (10.1016/0960-9776(95)90022-5) / BREAST / TYPE-1 GROWTH-FACTOR RECEPTORS - AN OVERVIEW OF RECENT DEVELOPMENTS by MASON S (1995)
  36. MCGUIRE W.L., MOL ENDOCRINOL 5, 157 (1991). (10.1210/mend-5-11-1571) / MOL ENDOCRINOL by MCGUIRE W.L. (1991)
  37. MELLON P.L., REGULATION OF TRANSCRIPTION BY CYCLIC AMP-DEPENDENT PROTEIN-KINASE, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 86, 4887 (1989). (10.1073/pnas.86.13.4887) / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA / REGULATION OF TRANSCRIPTION BY CYCLIC AMP-DEPENDENT PROTEIN-KINASE by MELLON P.L. (1989)
  38. METZGER D, CHARACTERIZATION OF THE AMINO-TERMINAL TRANSCRIPTIONAL ACTIVATION FUNCTION OF THE HUMAN ESTROGEN-RECEPTOR IN ANIMAL AND YEAST-CELLS, JOURNAL OF BIOLOGICAL CHEMISTRY 270, 9535 (1995). (10.1074/jbc.270.16.9535) / JOURNAL OF BIOLOGICAL CHEMISTRY / CHARACTERIZATION OF THE AMINO-TERMINAL TRANSCRIPTIONAL ACTIVATION FUNCTION OF THE HUMAN ESTROGEN-RECEPTOR IN ANIMAL AND YEAST-CELLS by METZGER D (1995)
  39. METZGER D, EFFECT OF ANTAGONISTS ON DNA-BINDING PROPERTIES OF THE HUMAN ESTROGEN-RECEPTOR IN-VITRO AND IN-VIVO, MOLECULAR ENDOCRINOLOGY 9, 579 (1995). / MOLECULAR ENDOCRINOLOGY / EFFECT OF ANTAGONISTS ON DNA-BINDING PROPERTIES OF THE HUMAN ESTROGEN-RECEPTOR IN-VITRO AND IN-VIVO by METZGER D (1995)
  40. MURPHY L.C., SEMIN CANCER BIOL 1, 305 (1990). / SEMIN CANCER BIOL by MURPHY L.C. (1990)
  41. PETECH S.L., SCIENCE 257, 1355 (1992). (10.1126/science.1382311) / SCIENCE by PETECH S.L. (1992)
  42. ROCHLITZ C.F., INCIDENCE OF ACTIVATING RAS ONCOGENE MUTATIONS ASSOCIATED WITH PRIMARY AND METASTATIC HUMAN-BREAST CANCER, CANCER RESEARCH 49, 357 (1989). / CANCER RESEARCH / INCIDENCE OF ACTIVATING RAS ONCOGENE MUTATIONS ASSOCIATED WITH PRIMARY AND METASTATIC HUMAN-BREAST CANCER by ROCHLITZ C.F. (1989)
  43. 10.1126/science.2470152
  44. TORA L, THE HUMAN ESTROGEN-RECEPTOR HAS 2 INDEPENDENT NONACIDIC TRANSCRIPTIONAL ACTIVATION FUNCTIONS, CELL 59, 477 (1989). (10.1016/0092-8674(89)90031-7) / CELL / THE HUMAN ESTROGEN-RECEPTOR HAS 2 INDEPENDENT NONACIDIC TRANSCRIPTIONAL ACTIVATION FUNCTIONS by TORA L (1989)
  45. TSAI M.J., MOLECULAR MECHANISMS OF ACTION OF STEROID/THYROID RECEPTOR SUPERFAMILY MEMBERS, ANNUAL REVIEW OF BIOCHEMISTRY 63, 451 (1994). (10.1146/annurev.bi.63.070194.002315) / ANNUAL REVIEW OF BIOCHEMISTRY / MOLECULAR MECHANISMS OF ACTION OF STEROID/THYROID RECEPTOR SUPERFAMILY MEMBERS by TSAI M.J. (1994)
  46. WASBURN T, MOL ENDOCRINOL 5, 235 (1991). (10.1210/mend-5-2-235) / MOL ENDOCRINOL by WASBURN T (1991)
  47. WEBSTER NJG, THE HORMONE-BINDING DOMAINS OF THE ESTROGEN AND GLUCOCORTICOID RECEPTORS CONTAIN AN INDUCIBLE TRANSCRIPTION ACTIVATION FUNCTION, CELL 54, 199 (1988). (10.1016/0092-8674(88)90552-1) / CELL / THE HORMONE-BINDING DOMAINS OF THE ESTROGEN AND GLUCOCORTICOID RECEPTORS CONTAIN AN INDUCIBLE TRANSCRIPTION ACTIVATION FUNCTION by WEBSTER NJG (1988)
Dates
Type When
Created 18 years, 10 months ago (Oct. 27, 2006, 2:19 p.m.)
Deposited 1 year, 7 months ago (Jan. 12, 2024, 4:37 p.m.)
Indexed 17 hours, 12 minutes ago (Aug. 30, 2025, 12:43 p.m.)
Issued 29 years, 8 months ago (Dec. 1, 1995)
Published 29 years, 8 months ago (Dec. 1, 1995)
Published Print 29 years, 8 months ago (Dec. 1, 1995)
Funders 0

None

@article{Kato_1995, title={Activation of the Estrogen Receptor Through Phosphorylation by Mitogen-Activated Protein Kinase}, volume={270}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.270.5241.1491}, DOI={10.1126/science.270.5241.1491}, number={5241}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Kato, Shigeaki and Endoh, Hideki and Masuhiro, Yoshikazu and Kitamoto, Takuya and Uchiyama, Shimami and Sasaki, Haruna and Masushige, Shoichi and Gotoh, Yukiko and Nishida, Eisuke and Kawashima, Hiroyuki and Metzger, Daniel and Chambon, Pierre}, year={1995}, month=dec, pages={1491–1494} }