The role of Shc and insulin-like qrowth factor 1 receptor in mediating the translocation of estrogen receptor a to the plasma membrane

被引:271
作者
Song, RX [1 ]
Barnes, CJ
Zhang, ZG
Bao, YD
Kumar, R
Santen, RJ
机构
[1] Univ Virginia, Sch Med, Dept Internal Med, Charlottesville, VA 22903 USA
[2] Univ Virginia, Sch Med, Biomol Res Facil, Charlottesville, VA 22903 USA
[3] Univ Texas, MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA
关键词
D O I
10.1073/pnas.0308334100
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Our previous studies demonstrated that l7beta-estradiol (E2) rapidly induces the interaction of estrogen receptor alpha (ERalpha) with the adapter protein Shc, the translocation of ERalpha to the cell membrane, and the formation of dynamic membrane structures in MCF-7 breast cancer cells. The present study examined how E2 causes ERalpha to translocate to the region of the plasma membrane and focused on mechanisms whereby Shc and the insulin-like growth factor-1 receptor (IGF-1R) mediate this process. Shc physically interacts with IGF-1R in the plasma membrane, and E2 activates IGF-1R. We reasoned that ERalpha, when bound to Shc, would be directed to the region of the plasma membrane by the same processes, causing membrane translocation of Shc. We confirmed that E2 rapidly induced IGF-1 R phosphorylation and demonstrated that E2 induced formation of a ternary protein complex among Shc, ERalpha, and IGF-1R. Knock down of Shc with a specific small inhibitory RNA decreased the association of ERalpha with IGF-1R by 87%, suggesting that Shc is a crucial molecule in the formation of this ternary complex. Confocal microscopy studies provided further confirmation of the functional roles of Shc and the IGF-1R in the translocation of ERalpha to the region of the membrane. Down-regulation of Shc, ERalpha, or IGF-1R with specific small inhibitory RNAs all blocked E2-induced mitogen-activated protein kinase phosphorylation. Together, our results demonstrate that Shc and IGF-1R serve as key elements in the translocation of ERalpha to the cell membrane and in the facilitation of ERalpha-mediated rapid E2 action.
引用
收藏
页码:2076 / 2081
页数:6
相关论文
共 35 条
  • [1] Heregulin regulates cytoskeletal reorganization and cell migration through the p21-activated kinase-1 via phosphatidylinositol-3 kinase
    Adam, L
    Vadlamudi, R
    Kondapaka, SB
    Chernoff, J
    Mendelsohn, J
    Kumar, R
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (43) : 28238 - 28246
  • [2] Structure and function of the type 1 insulin-like growth factor receptor
    Adams, TE
    Epa, VC
    Garrett, TPJ
    Ward, CW
    [J]. CELLULAR AND MOLECULAR LIFE SCIENCES, 2000, 57 (07) : 1050 - 1093
  • [3] Bartucci M, 2001, CANCER RES, V61, P6747
  • [4] PI3-kinase in concert with Src promotes the S-phase entry of oestradiol-stimulated MCF-7 cells
    Castoria, G
    Migliaccio, A
    Bilancio, A
    Di Domenico, M
    de Falco, A
    Lombardi, M
    Fiorentino, R
    Varricchio, L
    Barone, MV
    Auricchio, F
    [J]. EMBO JOURNAL, 2001, 20 (21) : 6050 - 6059
  • [5] Estrogen hits the surface
    Collins, P
    Webb, C
    [J]. NATURE MEDICINE, 1999, 5 (10) : 1130 - 1131
  • [6] Domains of the insulin-like growth factor I receptor required for the activation of extracellular signal-regulated kinases
    Dews, M
    Prisco, M
    Peruzzi, F
    Romano, G
    Morrione, A
    Baserga, R
    [J]. ENDOCRINOLOGY, 2000, 141 (04) : 1289 - 1300
  • [7] SHC BINDING TO NERVE GROWTH-FACTOR RECEPTOR IS MEDIATED BY THE PHOSPHOTYROSINE INTERACTION DOMAIN
    DIKIC, I
    BATZER, AG
    BLAIKIE, P
    OBERMEIER, A
    ULLRICH, A
    SCHLESSINGER, J
    MARGOLIS, B
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (25) : 15125 - 15129
  • [8] Estrogen-induced activation of Erk-1 and Erk-2 requires the G protein-coupled receptor homolog, GPR30, and occurs via trans-activation of the epidermal growth factor receptor through release of HB-EGF
    Filardo, EJ
    Quinn, JA
    Bland, KI
    Frackelton, AR
    [J]. MOLECULAR ENDOCRINOLOGY, 2000, 14 (10) : 1649 - 1660
  • [9] Nonnuclear actions of estrogen
    Ho, KJ
    Liao, JK
    [J]. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2002, 22 (12) : 1952 - 1961
  • [10] Uterine and vaginal organ growth requires epidermal growth factor receptor signaling from stroma
    Hom, YK
    Young, P
    Wiesen, JF
    Miettinen, PJ
    Derynck, R
    Werb, Z
    Cunha, GR
    [J]. ENDOCRINOLOGY, 1998, 139 (03) : 913 - 921