Stimulation of membrane-bound guanylate cyclase activity by 17-beta estradiol.
Estrogen is known to exert both long-term genomic and short-term nongenomic actions. The long-term genomic actions of estrogen are mediated by the binding of estrogen to its cytoplasmic/nuclear receptor that subsequently triggers the transcription of target genes. In contrast, little is known about the molecular basis of the nongenomic actions of estrogen. We have found that 17-beta estradiol activates membrane-bound guanylate cyclase and enhances atrial natriuretic factor (ANF)-stimulated guanylate cyclase activity in PC12 cell membranes. Membrane-bound guanylate cyclase, GC-A, contains an extracellular ANF-binding domain and an intracellular kinase-like domain plus catalytic domain. The kinase-like domain plus the catalytic domain of guanylate cyclase (GC-kc) can be expressed in E. Coli and functionally renatured. 17-beta estradiol also activates the bacteria expressed GC-kc, indicating that 17-beta estradiol can directly interact with membrane-bound guanylate cyclase. These results demonstrate that 17-beta estradiol exerts a non-genomic action on membrane-bound guanylate cyclase.
Chen
Z J
ZJ
Department of Medicine, Division of Hypertension, Case Western Reserve University, Cleveland, Ohio, 44106, USA.
Yu
L
L
Chang
C H
CH
D000818:Animals; D001665:Binding Sites; D020134:Catalytic Domain; D002462:Cell Membrane / Q000201:enzymology; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology; D004958:Estradiol / Q000494:pharmacology*; D006162:Guanylate Cyclase / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats
D004958:Estradiol; D006162:Guanylate Cyclase