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Sci. STKE, 19 November 2002
Vol. 2002, Issue 159, p. tw425
[DOI: 10.1126/stke.2002.159.tw425]


Steroid Hormones Linking Estrogen to MAPK

The actions of steroid hormones are beginning to be recognized as belonging to two classes: the classical genomic action mediated by activation of the transcriptional regulatory activity of the hormone receptor and rapid cytosolic effects of the hormone. Wong et al. identified a partner for the estrogen-bound estrogen receptor (ERβ) in a screen for proteins from MCF-7 cells that bound the receptor in a ligand-dependent manner. The protein, which they call MNAR, is substantially similar to, but not identical with, the proline, glutamic acid, leucine-rich domain (PELP1) protein that binds to the Src homology domain 2 (SH2) of the kinase Lck. MNAR expressed in Sf9 cells was able to interact with in vitro translated ERα, ERβ, androgen, and glucocorticoid receptors in a ligand-dependent fashion. In vitro, estrogen promoted the interaction between Src family kinases, MNAR, and ERα and these complexes were confirmed in MCF-7 cells. MNAR stimulated Src kinase activity in vitro, and this effect was further enhanced by the addition of estrogen-bound ERα. Src activity was also stimulated in MCF-7 cells. Overexpression of MNAR stimulated phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1 and ERK2), whereas inhibition of MNAR expression with antisense inhibited estrogen-stimulated ERK phosphorylation. Thus, MNAR appears to be a link between steroid receptors and the mitogen-activated protein kinase (MAPK) cascade.

C.-W. Wong, C. McNally, E. Nickbarg, B. S. Komm, B. J. Cheskis, Estrogen receptor-interacting protein that modulates it nongenomic activity-crosstalk with Src/Erk phosphorylation cascade. Proc. Natl. Acad. Sci. U.S.A. 99, 14783-14788 (2002). [Abstract] [Full Text]

Citation: Linking Estrogen to MAPK. Sci. STKE 2002, tw425 (2002).

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