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PMID:10749889

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Citation

Kahlert, S, Nuedling, S, van Eickels, M, Vetter, H, Meyer, R and Grohe, C (2000) Estrogen receptor alpha rapidly activates the IGF-1 receptor pathway. J. Biol. Chem. 275:18447-53

Abstract

Estrogen and insulin-like-growth factor 1 (IGF-1) are potent mitogenic stimuli that share important properties in the control of cellular proliferation. However, the coupling between the signaling cascades of estrogen receptors alpha and beta and the IGF-1 receptor (IGF-1R) is poorly understood. Therefore, we selectively transfected estrogen receptor alpha or beta in COS7 and HEK293 cells, which contain IGF-1R. In presence of estrogen receptor alpha but not beta, 17beta-estradiol (E2) rapidly induces phosphorylation of the IGF-1R and the extracellular signal-regulated kinases 1/2. Furthermore, upon stimulation with E2, estrogen receptor alpha but not beta bound rapidly to the IGF-1R in COS7 as well as L6 cells, which express all investigated receptors endogenously. Control experiments in the IGF-1R-deficient fibroblast cell line R(-) showed that after stimulation with E2 only estrogen receptor alpha bound to the transfected IGF-1R. Overexpression of dominant negative mitogen-activated protein kinases kinase inhibited this effect. Finally, estrogen receptor alpha but not beta is required to induce the activation of the estrogen receptor-responsive reporter ERE-LUC in IGF-1-stimulated cells. Taken together, these data demonstrate that ligand bound estrogen receptor alpha is required for rapid activation of the IGF-1R signaling cascade.

Links

PubMed Online version:10.1074/jbc.M910345199

Keywords

Animals; COS Cells; Cell Division; Cell Line; Electrophoresis, Polyacrylamide Gel; Estrogen Receptor alpha; Estrogen Receptor beta; Humans; Mice; Phosphorylation; Receptor, IGF Type 1/metabolism; Receptors, Estrogen/metabolism; Signal Transduction

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:ESR1

involved_in

GO:0007165: signal transduction

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:ESR2

involved_in

GO:0007165: signal transduction

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:ESR2

enables

GO:0003707: steroid hormone receptor activity

ECO:0000304: author statement supported by traceable reference used in manual assertion

F

Seeded From UniProt

complete

HUMAN:ESR2

involved_in

GO:0007165: signal transduction

ECO:0000304: author statement supported by traceable reference used in manual assertion


P

Seeded From UniProt

complete

HUMAN:IGF1R

enables

GO:0005010: insulin-like growth factor-activated receptor activity

ECO:0000304: author statement supported by traceable reference used in manual assertion

F

Seeded From UniProt

complete

HUMAN:IGF1R

involved_in

GO:0008284: positive regulation of cell population proliferation

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete


See also

References

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