Title

Vitamin D Blocks Estrogen Signaling through PKA

Document Type

Article

Publication Date

2012

Abstract

Abstract The hormone estrogen (E2) activates a CaM KK, CaM KI, and ERK pathway to promote proliferation of MCF-7 breast cancer cells. ERK activation is inhibited by cAMP and PKA in certain cells. PKA has numerous cellular substrates including CREB and CaM KK. PKA phosphorylation of CaM KK inhibits its activity and promotes its association with 14-3-3{gamma}. Therefore hormones that stimulate PKA activation may in turn block activation of CaM KK and ERK as well as cell proliferation. Our goal was to evaluate PKA’s ability to phosphorylate CaM KK and promote its subsequent binding to 14-3-3{gamma} in Vitamin D-treated cells. In addition we examined whether Vitamin D’s inhibition of E2-stimulated ERK activation in MCF-7 cells utilized PKA using the inhibitor, H-89. Our results suggest that activation of PKA with Vitamin D inhibits E2 stimulation of ERK activation and increases CaM KK phosphorylation. Vitamin D treatment of MCF-7 cells, but not E2, increased CaM KK association with endogenous 14-3- 3. Interestingly, Vitamin D induced phosphorylation of CaM KK and ERK inhibition were both reversed by H-89. Our results suggest that Vitamin D activation of PKA triggers the subsequent phosphorylation and inhibition of CaM KK through its association with 14-3-3 preventing CaM KK from activating ERK in MCF-7 cells.

Comments

Amanda P. Ankeny and Schmitt, J. M.; “Vitamin D Blocks Estrogen Signaling through PKA ”, The FASEB Journal, American Society for Biochemistry and Molecular Biology, Vol. 26, 575.1, 2012.

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