Epidermal growth factor directs sex-specific steroid signaling through Src activation

Taro D Hitosugi, Kazuki Sasaki, Moritoshi Sato, Yoshiko Suzuki, Yoshio Umezawa

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Estrogens and androgens exert many biological effects that do not require interactions of their receptors with chromosomal DNA. However, it has been a long-standing question how the sex steroid receptors provoke signal transduction outside the nucleus. Here we have shown that epidermal growth factor (EGF) directs sex-specific steroid signaling through Src activation. Wehave revealed that estrogen (E2)-induced Src activation takes place in, not only plasma, but also endomembranes. This was found ascribed to the existence of EGF and the occurrence of EGF receptor (EGFR)-involved endocytosis of estrogen receptor together with Src. EGFR, estrogen receptor, and Src were found to form a complex upon E2 stimulation. The cell growth of breast cancer-derived MCF-7 cells was found to remarkably increase through the above EGF-involved estrogen-signaling process. In contrast, the androgen 5 α-dihydrotestosterone-induced Src activation occurs only in the plasma membrane free from the interaction of EGFR with androgen receptor, irrespective of EGF. The cell growth occurred only moderately as a result. The spatial difference in Src activation between E2 and 5α-dihydrotestosterone may be responsible for the different extent of observed cell growth.

Original languageEnglish (US)
Pages (from-to)10697-10706
Number of pages10
JournalJournal of Biological Chemistry
Volume282
Issue number14
DOIs
StatePublished - Apr 6 2007
Externally publishedYes

Fingerprint

Epidermal Growth Factor
Cell growth
Chemical activation
Steroids
Epidermal Growth Factor Receptor
Estrogens
Dihydrotestosterone
Estrogen Receptors
Androgens
Growth
Signal transduction
Steroid Receptors
MCF-7 Cells
Androgen Receptors
Cell membranes
Endocytosis
Signal Transduction
Cell Membrane
Breast Neoplasms
Plasmas

ASJC Scopus subject areas

  • Biochemistry

Cite this

Epidermal growth factor directs sex-specific steroid signaling through Src activation. / Hitosugi, Taro D; Sasaki, Kazuki; Sato, Moritoshi; Suzuki, Yoshiko; Umezawa, Yoshio.

In: Journal of Biological Chemistry, Vol. 282, No. 14, 06.04.2007, p. 10697-10706.

Research output: Contribution to journalArticle

Hitosugi, Taro D ; Sasaki, Kazuki ; Sato, Moritoshi ; Suzuki, Yoshiko ; Umezawa, Yoshio. / Epidermal growth factor directs sex-specific steroid signaling through Src activation. In: Journal of Biological Chemistry. 2007 ; Vol. 282, No. 14. pp. 10697-10706.
@article{995a0af12dd643b39648caddc3b3e58d,
title = "Epidermal growth factor directs sex-specific steroid signaling through Src activation",
abstract = "Estrogens and androgens exert many biological effects that do not require interactions of their receptors with chromosomal DNA. However, it has been a long-standing question how the sex steroid receptors provoke signal transduction outside the nucleus. Here we have shown that epidermal growth factor (EGF) directs sex-specific steroid signaling through Src activation. Wehave revealed that estrogen (E2)-induced Src activation takes place in, not only plasma, but also endomembranes. This was found ascribed to the existence of EGF and the occurrence of EGF receptor (EGFR)-involved endocytosis of estrogen receptor together with Src. EGFR, estrogen receptor, and Src were found to form a complex upon E2 stimulation. The cell growth of breast cancer-derived MCF-7 cells was found to remarkably increase through the above EGF-involved estrogen-signaling process. In contrast, the androgen 5 α-dihydrotestosterone-induced Src activation occurs only in the plasma membrane free from the interaction of EGFR with androgen receptor, irrespective of EGF. The cell growth occurred only moderately as a result. The spatial difference in Src activation between E2 and 5α-dihydrotestosterone may be responsible for the different extent of observed cell growth.",
author = "Hitosugi, {Taro D} and Kazuki Sasaki and Moritoshi Sato and Yoshiko Suzuki and Yoshio Umezawa",
year = "2007",
month = "4",
day = "6",
doi = "10.1074/jbc.M610444200",
language = "English (US)",
volume = "282",
pages = "10697--10706",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "14",

}

TY - JOUR

T1 - Epidermal growth factor directs sex-specific steroid signaling through Src activation

AU - Hitosugi, Taro D

AU - Sasaki, Kazuki

AU - Sato, Moritoshi

AU - Suzuki, Yoshiko

AU - Umezawa, Yoshio

PY - 2007/4/6

Y1 - 2007/4/6

N2 - Estrogens and androgens exert many biological effects that do not require interactions of their receptors with chromosomal DNA. However, it has been a long-standing question how the sex steroid receptors provoke signal transduction outside the nucleus. Here we have shown that epidermal growth factor (EGF) directs sex-specific steroid signaling through Src activation. Wehave revealed that estrogen (E2)-induced Src activation takes place in, not only plasma, but also endomembranes. This was found ascribed to the existence of EGF and the occurrence of EGF receptor (EGFR)-involved endocytosis of estrogen receptor together with Src. EGFR, estrogen receptor, and Src were found to form a complex upon E2 stimulation. The cell growth of breast cancer-derived MCF-7 cells was found to remarkably increase through the above EGF-involved estrogen-signaling process. In contrast, the androgen 5 α-dihydrotestosterone-induced Src activation occurs only in the plasma membrane free from the interaction of EGFR with androgen receptor, irrespective of EGF. The cell growth occurred only moderately as a result. The spatial difference in Src activation between E2 and 5α-dihydrotestosterone may be responsible for the different extent of observed cell growth.

AB - Estrogens and androgens exert many biological effects that do not require interactions of their receptors with chromosomal DNA. However, it has been a long-standing question how the sex steroid receptors provoke signal transduction outside the nucleus. Here we have shown that epidermal growth factor (EGF) directs sex-specific steroid signaling through Src activation. Wehave revealed that estrogen (E2)-induced Src activation takes place in, not only plasma, but also endomembranes. This was found ascribed to the existence of EGF and the occurrence of EGF receptor (EGFR)-involved endocytosis of estrogen receptor together with Src. EGFR, estrogen receptor, and Src were found to form a complex upon E2 stimulation. The cell growth of breast cancer-derived MCF-7 cells was found to remarkably increase through the above EGF-involved estrogen-signaling process. In contrast, the androgen 5 α-dihydrotestosterone-induced Src activation occurs only in the plasma membrane free from the interaction of EGFR with androgen receptor, irrespective of EGF. The cell growth occurred only moderately as a result. The spatial difference in Src activation between E2 and 5α-dihydrotestosterone may be responsible for the different extent of observed cell growth.

UR - http://www.scopus.com/inward/record.url?scp=34249306702&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34249306702&partnerID=8YFLogxK

U2 - 10.1074/jbc.M610444200

DO - 10.1074/jbc.M610444200

M3 - Article

C2 - 17284441

AN - SCOPUS:34249306702

VL - 282

SP - 10697

EP - 10706

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 14

ER -